New purine derivatives, the preparation thereof and their use as pharmaceutical compositions

ABSTRACT

The invention relates to new purine derivatives of general formula  
                 
 
     wherein R 1  to R 4  are defined as in the claims, the tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV), the preparation thereof, the use thereof for the prevention or treatment of diseases or conditions associated with an increased DPP-IV activity or capable of being prevented or alleviated by reducing the DPP-IV activity, particularly type I or type II diabetes mellitus, the pharmaceutical compositions containing a compound of general formula (I) or a physiologically acceptable salt thereof as well as processes for the preparation thereof.

RELATED APPLICATIONS

[0001] Benefit of U.S. Provisional Application Serial No. 60/408,021,filed on Sep. 4, 2002 and German application DE 102 38 477 filed Aug.22, 2002 is hereby claimed.

FIELD OF THE INVENTION

[0002] The present invention relates to substituted purines of generalformula

[0003] the tautomers, the stereoisomers, the mixtures, the prodrugsthereof and the salts thereof, particularly the physiologicallyacceptable salts thereof with inorganic or organic acids or bases whichhave valuable pharmacological properties, particularly an inhibitingeffect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV),the preparation thereof, the use thereof for the prevention or treatmentof diseases or conditions associated with an increased DPP-IV activityor capable of being prevented or alleviated by reducing the DPP-IVactivity, particularly type I or type II diabetes mellitus, thepharmaceutical compositions containing a compound of general formula (I)or a physiologically acceptable salt thereof as well as processes forthe preparation thereof.

[0004] In the above formula I

[0005] R¹ denotes a hydrogen atom,

[0006] a C₁₋₈-alkyl group,

[0007] a C₃₋₈-alkenyl group,

[0008] a C₃₋₄-alkenyl group which is substituted by aC₁₋₂-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C₃₋₈-alkynylgroup,

[0009] a C₁₋₆-alkyl group substituted by a group R_(a), where R_(a)denotes a C₃₋₇-cycloalkyl, heteroaryl, cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl,4-methylpiperazin-1-ylcarbonyl or 4-ethylpiperazin-1-ylcarbonyl group,

[0010] a C₁₋₆-alkyl group substituted by a phenyl group, where thephenyl ring is substituted by the groups R¹⁰ to R¹⁴ and

[0011] R¹⁰ denotes a hydrogen atom,

[0012] a fluorine, chlorine, bromine or iodine atom,

[0013] a C₁₋₄-alkyl, hydroxy or C₁₋₄-alkyloxy group,

[0014] a nitro, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino,cyan-C₁₋₃-alkylamino, N-(cyan-C₁₋₃-alkyl)-N-(C₁₋₃-alkyl)-amino,C₁-3-alkyloxy-carbonyl-C₁₋₃-alkylamino, pyrrolidin-1-yl, piperidin-1-yl,morpholin-4-yl, piperazin-1-yl or 4-(C₁₋₃-alkyl)-piperazin-1-yl group,

[0015] a formylamino, C₁₋₃-alkyl-carbonylamino,C₃₋₆-cycloalkyl-carbonylamino, C₃₋₆-cycloalkyl-C₁₋₃-alkyl-carbonylamino,arylcarbonylamino, aryl-C₁₋₃-alkyl-carbonyl-amino,C₁₋₃-alkyloxy-carbonylamino, aminocarbonylamino,C₁₋₃-alkyl-amino-carbonylamino, di-(C₁₋₃-alkyl)-aminocarbonylamino,pyrrolidin-1-yl-carbonylamino, piperidin-1-yl-carbonylamino,morpholin-4-yl-carbonylamino, piperazin-1-yl-carbonylamino or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonylamino, C₁₋₃-alkyl-sulphonylamino,bis-(C₁₋₃-alkylsulphonyl)-amino, aminosulphonylamino,C₁₋₃-alkyl-amino-sulphonylamino, di-(C₁₋₃-alkyl)-amino-sulphonylamino,pyrrolidin-1-yl-sulphonylamino, piperidin-1-yl-sulphonylamino,morpholin-4-yl-sulphonylamino, piperazin-1-yl-sulphonylamino or 4-(C₁3-alkyl)-piperazin-1-yl-sulphonylamino,(C₁₋₃-alkylamino)-thiocarbonylamino,(C₁₋₃-alkyloxy-carbonylamino)-carbonylamino, arylsulphonylamino oraryl-C₁₋₃-alkyl-sulphonylamino group,

[0016] an N-(C₁₋₃-alkyl)-formylamino,N-(C₁₋₃-alkyl)-N-(C₁₋₃-alkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(C₃₋₆-cycloalkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(C₃₋₆-cycloalkyl-C₁₋₃-alkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(arylcarbonyl)-amino,N-(C₁₋₃-alkyl)-N-(aryl-C₁₋₃-alkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(C₁₋₃-alkyloxy-carbonyl)-amino,N-(aminocarbonyl)-N-(C₁₋₃-alkyl)-amino,N-(C₁₋₃-alkyl-aminocarbonyl)-N-(C₁₋₃-alkyl)-amino,N-[di-(C₁₋₃-alkyl)aminocarbonyl]-N-(C₁₋₃-alkyl)-amino,N-(C₁₋₃-alkyl)-N-(C₁₋₃-alkyl-sulphonyl)-amino,N-(C₁₋₃-alkyl)-N-(arylsulphonyl)-amino orN-(C₁₋₃-alkyl)-N-(aryl-C₁₋₃-alkyl-sulphonyl)-amino group,

[0017] a 2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl,2,5-dioxo-imidazolidin-1-yl or 2-oxo-hexahydropyrimidin-1-yl groupwherein the nitrogen atom in the 3 position may be substituted in eachcase by a methyl or ethyl group,

[0018] a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,C₁₋₃-alkyl-aminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl,morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl group,

[0019] a C₁₋₃-alkyl-carbonyl or an arylcarbonyl group,

[0020] a carboxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl,cyano-C₁₋₃-alkyl, aminocarbonyl-C₁₋₃-alkyl,C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyl,di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyl,pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyl, piperidin-1-yl-carbonyl-C₁₋₃-alkyl,morpholin-4-yl-carbonyl-C₁₋₃-alkyl, piperazin-1-yl-carbonyl-C₁₋₃-alkylor 4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyl group,

[0021] a carboxy-C₁₋₃-alkyloxy, C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyloxy,cyano-C₁₋₁₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy,C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyloxy,di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy,pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyl-oxy,piperidin-1-yl-carbonyl-C₁₋₃-alkyloxy,morpholin-4-yl-carbonyl-C₁₋₃-alkyl-oxy,piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy group,

[0022] a hydroxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl,pyrrolidin-1-yl-C₁_₃-alkyl, piperidin-1-yl-C₁₋₃-alkyl,morpholin-4-yl-C₁₋₃-alkyl, piperazin-1-yl-C₁₋₃-alkyl,4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyl group,

[0023] a hydroxy-C₁₋₃-alkyloxy, C₁₋₃-alkyloxy-C₁₋₃-alkyloxy,C₁₋₃-alkylsulphanyl-C₁₋₃-alkyloxy, C₁₋₃-alkylsulphinyl-C₁₋₃-alkyloxy,C₁₋₃-alkylsulphonyl-C₁₋₃-alkyloxy, amino-C₁₋₃-alkyloxy,C₁₋₃-alkylamino-C₁₋₃-alkyloxy, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyloxy,pyrrolidin-1-yl-C₁₋₃-alkyloxy, piperidin-1-yl-C₁₋₃-alkyloxy,morpholin-4-yl-C₁₋₃-alkyloxy, piperazin-1-yl-C₁₋₃-alkyloxy,4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyloxy group,

[0024] a mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkysulphinyl,C₁₋₃-alkylsulphonyl, C₁₋₃-alkylsulphonyloxy, arylsulphonyloxy,trifluoromethylsulphanyl, trifluoromethylsulphinyl ortrifluoromethylsulphonyl group,

[0025] a sulpho, aminosulphonyl, C₁₋₃-alkyl-aminosulphonyl,di-(C₁₋₃-alkyl)-amino-sulphonyl, pyrrolidin-1-yl-sulphonyl,piperidin-1-yl-sulphonyl, morpholin-4-yl-sulphonyl,piperazin-1-yl-sulphonyl or 4-(C₁₋₃-alkyl)-piperazin-1-yl-sulphonylgroup,

[0026] a methyl or methoxy group substituted by 1 to 3 fluorine atoms,

[0027] an ethyl or ethyloxy group substituted by 1 to 5 fluorine atoms,

[0028] a C₂₋₄-alkenyl or C₂₋₄-alkynyl group,

[0029] a C₃₋₄-alkenyloxy or C₃₋₄-alkynyloxy group,

[0030] a C₃₋₆-cycloalkyl or C₃₋₆-cycloalkyloxy group,

[0031] a C₃₋₆-cycloalkyl-C₁₋₃-alkyl or C₃₋₆-cycloalkyl-C₁₋₃-alkyloxygroup or

[0032] an aryl, aryloxy, aryl-C₁₋₃-alkyl or aryl-C₁₋₃-alkyloxy group,

[0033] R¹¹ and R¹², which may be identical or different, in each caserepresent a hydrogen atom, a fluorine, chlorine, bromine or iodine atom,a C₁₋₃-alkyl, trifluoromethyl, hydroxy, C₁₋₃-alkyloxy or cyano group, or

[0034] R¹¹ together with R¹², if they are bound to adjacent carbonatoms, also represent a methylenedioxy, difluoromethylenedioxy or astraight-chain C₃₋₅-alkylene group and

[0035] R¹³ and R¹⁴, which may be identical or different, in each caserepresent a hydrogen atom, a fluorine, chlorine or bromine atom, atrifluoromethyl, C₁₋₃-alkyl or C₁₋₃-alkyloxy group,

[0036] a phenyl-C₁₋₄-alkyl group wherein the alkyl moiety is substitutedby a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,C₁₋₃-alkyl-aminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl,morpholin-4-yl-carbonyl-group and the phenyl moiety is substituted bythe groups R¹⁰ to R¹⁴, while R¹⁰ to R¹⁴ are as hereinbefore defined,

[0037] a phenyl group substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴ are as hereinbefore defined,

[0038] a phenyl-C₂₋₃-alkenyl group wherein the phenyl moiety issubstituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are ashereinbefore defined,

[0039] a phenyl-(CH₂)_(m)—A—(CH₂)_(n)—group wherein the phenyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore definedand

[0040] A represents a carbonyl group, m represents the number 0, 1 or 2and n represents the number 1, 2 or 3,

[0041] a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore definedand the methyl moiety is substituted by a C₁₋₃-alkyl group,

[0042] a phenyl-(CH₂)_(m)—B—(CH₂)_(n)—group wherein the phenyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, m and n are as hereinbeforedefined and

[0043] B denotes a methylene group which is substituted by a hydroxy,C₁₋₃-alkyloxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, mercapto,C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl or C₁₋₃-alkylsulphonyl groupand is optionally additionally substituted by a methyl or ethyl group,

[0044] a naphthyl-C₁₋₃-alkyl group wherein the naphthyl moiety issubstituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are ashereinbefore defined,

[0045] a naphthyl-(CH₂)_(m)—A—(CH₂)_(n)—group wherein the naphthylmoiety is substituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, A, m and n are ashereinbefore defined,

[0046] a naphthyl-(CH₂)_(m)—B—(CH₂)_(n)—group wherein the naphthylmoiety is substituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, B, m and n are ashereinbefore defined,

[0047] a [1,4]naphthoquinon-2-yl, chromen-4-on-3-yl, 1-oxoindan-2-yl,1,3-dioxoindan-2-yl or 2,3-dihydro-3-oxo-benzofuran-2-yl group,

[0048] a heteroaryl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and n are ashereinbefore defined,

[0049] a heteroaryl-(CH₂)_(m)—B—(CH₂)_(n) group where B, m and n are ashereinbefore defined,

[0050] a C₁₋₆-alkyl-A—(CH₂)_(n) group where A and n are as hereinbeforedefined,

[0051] a C₃₋₇-cycloalkyl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and nare as hereinbefore defined,

[0052] a C₃₋₇-cycloalkyl-(CH₂)_(m)—B—(CH₂)_(n) group where B, m and nare as hereinbefore defined,

[0053] an R²¹—A—(CH₂)_(n)—group wherein R²¹ denotes aC₁₋₃-alkyloxycarbonyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl,di-(C₁₋₃-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl,piperidin-1-yl-carbonyl or morpholin-4-yl-carbonyl,piperazin-1-yl-carbonyl, 4-methylpiperazin-1-yl-carbonyl or4-ethylpiperazin-1-yl-carbonyl group and A and n are as hereinbeforedefined,

[0054] a phenyl-(CH₂)_(m)—D—C₁₋₃-alkyl group wherein the phenyl moietyis substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ and m are asmentioned hereinbefore and D denotes an oxygen or sulphur atom, animino, C₁₋₃-alkylimino, sulphinyl or sulphonyl group,

[0055] a naphthyl-(CH₂)_(m)—D—C₁₋₃-alkyl group wherein the naphthylmoiety is substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, D andm are as mentioned hereinbefore,

[0056] a C₂₋₆-alkyl group substituted by a group R_(b), where

[0057] R_(b) is isolated from the cyclic nitrogen atom in the 1 positionof the purine skeleton by at least two carbon atoms and

[0058] R_(b) denotes a hydroxy, C₁₋₃-alkyloxy, mercapto,C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, amino,C₁₋₃-alkyl-carbonylamino, C₃₋₆-cycloalkyl-carbonyl-amino,arylcarbonylamino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino,pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-(C₁₋₃-alkyl)-piperazin-1-yl group,

[0059] a C₃₋₆-cycloalkyl group,

[0060] or an amino or arylcarbonylamino group,

[0061] R² denotes a hydrogen atom,

[0062] a C₁₋₈-alkyl group,

[0063] a C₃₋₈-alkenyl group,

[0064] a C₃₋₄-alkenyl group which is substituted by aC₁₋₂-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonylormorpholin-4-ylcarbonyl group,

[0065] a C₃₋₈-alkynyl group,

[0066] a C₃₋₆-cycloalkyl group,

[0067] a C₁₋₆-alkyl group substituted by a group R_(a), where R_(a) isas hereinbefore defined,

[0068] a phenyl group which is substituted by R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴ are as hereinbefore defined,

[0069] a C₁₋₆-alkyl group substituted by a phenyl group, wherein thephenyl ring is substituted by the groups R¹⁰ to R¹⁴ and R¹⁰ to R¹⁴ areas hereinbefore defined,

[0070] a phenyl-C₁₋₄-alkyl group wherein the alkyl moiety is substitutedby a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,C₁₋₃-alkyl-aminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl,morpholin-4-yl-carbonyl group and the phenyl moiety is substituted bythe groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined,

[0071] a phenyl-C₂₋₃-alkenyl group wherein the phenyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined,

[0072] a heteroaryl group,

[0073] a phenyl-(CH₂)_(m)—A or phenyl-(CH₂)_(m)—A—(CH₂)_(n) groupwherein the phenyl moiety is substituted in each case by R¹⁰ to R¹⁴,while A, R¹⁰ to R¹⁴, m and n are as hereinbefore defined,

[0074] a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore definedand the methyl moiety is substituted by a C₁₋₃-alkyl group,

[0075] a phenyl-(CH₂)_(m)—B or phenyl-(CH₂)_(m)—B—(CH₂)_(n) groupwherein the phenyl moiety is substituted in each case by R¹⁰ to R¹⁴,while B, R¹⁰ to R¹⁴, m and n are as hereinbefore defined,

[0076] a naphthyl-C₁₋₃-alkyl group wherein the naphthyl moiety issubstituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are ashereinbefore defined,

[0077] a naphthyl-(CH₂)_(m)—A or naphthyl-(CH₂)_(m)—A—(CH₂)_(n) groupwherein the naphthyl moiety is substituted in each case by R¹⁰ to R¹⁴,where R¹⁰ to R¹⁴, A, m and n are as hereinbefore defined,

[0078] a naphthyl-(CH₂)_(m)—B or naphthyl-(CH₂)_(m)—B—(CH₂)_(n) groupwherein the naphthyl moiety is substituted in each case by R¹⁰ to R¹⁴,where R¹⁰ to R¹⁴, B, m and n are as hereinbefore defined,

[0079] a heteroaryl-(CH₂)_(m)—A or heteroaryl-(CH₂)_(m)—A—(CH₂)_(n)group where A, m and n are as hereinbefore defined,

[0080] a heteroaryl-(CH₂)_(m)—B or heteroaryl-(CH₂)_(m)—B—(CH₂)_(n)group where B, m and n are as hereinbefore defined,

[0081] a C₁₋₆-alkyl-A or C₁₋₆-alkyl-A—(CH₂)_(n) group where A and n areas hereinbefore defined, a C₃₋₇-cycloalkyl-(CH₂)_(m)—A orC₃₋₇-cycloalkyl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and n are ashereinbefore defined,

[0082] a C₃₋₇-cycloalkyl-(CH₂)_(m)—B orC₃₋₇-cycloalkyl-(CH₂)_(m)—B—(CH₂)_(n) group where B, m and n are ashereinbefore defined,

[0083] an R²¹-A—(CH₂)_(n) group wherein R²¹, A and n are as hereinbeforedefined,

[0084] a phenyl-(CH₂)_(m)—D—C₁₋₃-alkyl group wherein the phenyl moietyis substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, D and m areas mentioned hereinbefore,

[0085] a naphthyl-(CH₂)_(m)—D—C₁₋₃-alkyl group wherein the naphthylmoiety is substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, D andm are as mentioned hereinbefore,

[0086] a C₁₋₆-alkyl group substituted by a group R_(b), where R_(b) isas hereinbefore defined,

[0087] a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,C₁₋₃-alkylamino-carbonyl, di-(C₁₋₃-alkyl)-amino-carbonyl,pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl,piperazin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl or4-ethylpiperazin-1-ylcarbonyl group,

[0088] an amino, C₁₋₆-alkylamino or di-(C₁₋₆-alkyl)-amino group,

[0089] an amino group substituted by the groups R¹⁵ and R¹⁶ wherein

[0090] R¹⁵ denotes a hydrogen atom or a C₁₋₆-alkyl group and

[0091] R¹⁶ denotes a C₁₋₆-alkyl group which is substituted by R_(a),where R_(a) is as hereinbefore defined,

[0092] an amino group substituted by the groups R¹⁵ and R¹⁷ wherein

[0093] R¹⁵ is as hereinbefore defined and

[0094] R¹⁷ denotes a C₂₋₆-alkyl group which is substituted by a hydroxy,C₁₋₃-alkyloxy, aryloxy, mercapto, C₁₋₃-alkylsulphanyl,C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, C₁₋₃-alkylsulphonylamino,arylsulphanyl, arylsulphinyl, arylsulphonyl, arylsulphonylamino,C₁₋₃-alkyl-carbonylamino, C₃₋₆-cycloalkyl-carbonylamino,arylcarbonylamino, C₁₋₃-alkyl-oxycarbonylamino, aminocarbonylamino,C₁₋₃-alkyl-aminocarbonylamino, di-(C₁₋₃-alkyl)-aminocarbonylamino,amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, pyrrolidin-1-yl,piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-(C₁₋₃-alkyl)-piperazin-1-yl group,

[0095] a C₃₋₆-cycloalkylamino orN-(C₃₋₆-cycloalkyl)-N-(C₁₋₃-alkyl)-amino group,

[0096] a phenylamino or N-(phenyl)-N-(C₁₋₃-alkyl)-amino group whereinthe phenyl moiety is substituted in each case by R¹⁰ to R¹⁴, where R¹⁰to R¹⁴ are as hereinbefore defined,

[0097] a phenyl-C₁₋₆-alkylamino orN-(phenyl-C₁₋₆-alkyl)-N-(C₁₋₃-alkyl)-amino group wherein the phenylmoiety is substituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ areas hereinbefore defined,

[0098] a naphthylamino or N-(naphthyl)-N-(C₁₋₃-alkyl)-amino group,

[0099] a naphthyl-C₁₋₆-alkylamino orN-(naphthyl-C₁₋₆-alkyl)-N-(C₁₋₃-alkyl)-amino group,

[0100] a heteroarylamino or N-(heteroaryl)-N-(C₁₋₃-alkyl)-amino group,

[0101] a pyrrolidin-1-yl, piperidin-1-yl, homopiperidin-1-yl,morpholin-4-yl, homomorpholin-4-yl, piperazin-1-yl,4-(C₁₋₃-alkyl)-piperazin-1-yl, homopiperazin-1-yl or 4-(C₁I₃-alkyl)-homopiperazin-1-yl group, or

[0102] a C₁₋₆-alkyloxy, C₃₋₆-cycloalkyloxy orC₃₋₆-cycloalkyl-C₁₋₆-alkyloxy group,

[0103] a C₁₋₆-alkylsulphanyl, C₃₋₆-cycloalkylsulphanyl orC₃₋₆-cycloalkyl-C₁₋₆-alkylsulphanyl group,

[0104] a phenyloxy or phenylsulphanyl group wherein the phenyl moiety issubstituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are ashereinbefore defined,

[0105] a phenyl-C₁₋₁₆-alkyloxy or phenyl-C₁₋₁₆-alkylsulphanyl groupwherein the phenyl moiety is substituted in each case by R¹⁰ to R¹⁴,where R¹⁰ to R¹⁴ are as hereinbefore defined,

[0106] a naphthyloxy or a naphthylsulphanyl group wherein the naphthylmoiety is substituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ areas hereinbefore defined,

[0107] a naphthyl-C₁₋₆-alkyloxy or naphthyl-C₁₋₆-alkylsulphanyl groupwherein the naphthyl moiety is substituted in each case by R¹⁰ to R¹⁴,where R¹⁰ to R¹⁴ are as hereinbefore defined,

[0108] a heteroaryloxy or heteroarylsulphanyl group or

[0109] a heteroaryl-C₁₋₆-alkyloxy or heteroaryl-C₁₋₆-alkylsulphanylgroup,

[0110] R³ denotes a C₁₋₈-alkyl group,

[0111] a C₁₋₁₄-alkyl group substituted by the group R_(c), where

[0112] R_(c) denotes a C₃₋₇-cycloalkyl group optionally substituted byone or two C₁₋₃-alkyl groups,

[0113] a C₅₋₇-cycloalkenyl group optionally substituted by one or twoC₁₋₃-alkyl groups, an aryl group or

[0114] a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, whilethe above-mentioned heterocyclic groups may each be substituted by oneor two C₁₋₃-alkyl groups or by a fluorine, chlorine, bromine or iodineatom or by a trifluoromethyl, cyano or C₁₋₃-alkyloxy group,

[0115] a C₃₋₈-alkenyl group,

[0116] a C₃₋₆-alkenyl group substituted by a fluorine, chlorine orbromine atom or a trifluoromethyl group,

[0117] a C₃₋₈-alkynyl group,

[0118] an aryl group or

[0119] an aryl-C₂₋₄-alkenyl group, and

[0120] R⁴ denotes an azetidin-1-yl or pyrrolidin-1-yl group which issubstituted in the 3 position by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)-amino group and may additionally be substituted by oneor two C₁₋₃-alkyl groups,

[0121] a piperidin-1-yl or hexahydroazepin-1-yl group which issubstituted in the 3 position or in the 4 position by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)amino group and may additionally besubstituted by one or two C₁₋₃-alkyl groups,

[0122] a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl-moietyis additionally substituted by an aminocarbonyl,C₁₋₂-alkyl-aminocarbonyl, di-(C₁₋₂-alkyl)-aminocarbonyl,pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl,thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl,piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group,

[0123] a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moietyis additionally substituted in the 4 position or 5 position by a hydroxyor methoxy group,

[0124] a 3-amino-piperidin-1-yl group wherein the methylene group isreplaced in the 2 position or 6 position by a carbonyl group,

[0125] a piperidin-1-yl or hexahydroazepin-1-yl- group substituted inthe 3 position by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-aminogroup, wherein two hydrogen atoms on the carbon skeleton of thepiperidin-1-yl or hexahydroazepin-1-yl group are each replaced by astraight-chain alkylene bridge, this bridge containing 2 to 5 carbonatoms if the two hydrogen atoms are on the same carbon atom, or 1 to 4carbon atoms if the hydrogen atoms are on adjacent carbon atoms, or 1 to4 carbon atoms if the hydrogen atoms are on carbon atoms which areseparated by one atom, or 1 to 3 carbon atoms if the hydrogen atoms areon carbon atoms which are separated by two atoms,

[0126] an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl orhexahydroazepin-1-yl group which is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0127] a piperazin-1-yl or [1,4]diazepan-1-yl group optionallysubstituted on the carbon skeleton by one or two C I₃-alkyl groups,

[0128] a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or5-imino-[1,4]diazepan-1-yl group optionally substituted on the carbonskeleton by one or two C₁₋₃-alkyl groups,

[0129] a [1,4]diazepan-1-yl group optionally substituted by one or two CI₃-alkyl groups, which is substituted in the 6 position by an aminogroup,

[0130] a C₃₋₇-cycloalkyl group which is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,

[0131] a C₃₋₇-cycloalkyl group which is substituted by anamino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0132] a C₃₋₇-cycloalkyl-C I₂-alkyl group wherein the cycloalkyl moietyis substituted by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-aminogroup,

[0133] a C₃₋₇-cycloalkyl-C I₂-alkyl group wherein the cycloalkyl moietyis substituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0134] a C₃₋₇-cycloalkylamino group wherein the cycloalkyl moiety issubstituted by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,while the two nitrogen atoms on the cycloalkyl moiety are separated fromone another by at least two carbon atoms,

[0135] an N-(C₃₋₇-cycloalkyl)-N-(C₁₋₃-alkyl)-amino group wherein thecycloalkyl moiety is substituted by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)-amino group, while the two nitrogen atoms on thecycloalkyl moiety are separated from one another by at least two carbonatoms,

[0136] a C₃₋₇-cycloalkylamino group wherein the cycloalkyl moiety issubstituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0137] an N-(C₃₋₇-cycloalkyl)-N-(C₁₋₃-alkyl)-amino group wherein thecycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0138] a C₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino group wherein the cycloalkylmoiety is substituted by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)-amino group,

[0139] an N-(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N-(C₁₋₂-alkyl)-amino groupwherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,

[0140] a C₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino group wherein the cycloalkylmoiety is substituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkylor a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0141] an N-(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N-(C₁₋₂-alkyl)-amino groupwherein the cycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,

[0142] an R¹⁹-C₂₋₄-alkylamino group wherein R¹⁹ is separated from thenitrogen atom of the C₂₋₄-alkylamino moiety by at least two carbon atomsand

[0143] R¹⁹ denotes an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-aminogroup,

[0144] an R¹⁹-C₂₋₄-alkylamino group wherein the nitrogen atom of theC₂₋₄-alkylamino moiety is substituted by a C₁₋₃-alkyl group and R¹⁹ isseparated from the nitrogen atom of the C₂₋₄-alkylamino moiety by atleast two carbon atoms, where R¹⁹ is as hereinbefore defined,

[0145] an amino group substituted by the group R²⁰ wherein

[0146] R²⁰ denotes an azetidin-3-yl, azetidin-2-ylmethyl,azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl,pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yl,piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethylgroup, while the groups mentioned for R²⁰ may each be substituted by oneor two C₁₋₃-alkyl groups,

[0147] an amino group substituted by the group R²⁰ and a C₁₋₃-alkylgroup wherein R²⁰ is as hereinbefore defined, while the groups mentionedfor R²⁰ may each be substituted by one or two C₁₋₃-alkyl groups,

[0148] an R¹⁹-C₃₋₄-alkyl group wherein the C₃₋₄-alkyl moiety isstraight-chained and may additionally be substituted by one or twoC₁₋₃-alkyl groups, where R¹⁹ is as hereinbefore defined,

[0149] a 3-amino-2-oxo-piperidin-5-yl or3-amino-2-oxo-1-methyl-piperidin-5-yl group,

[0150] a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl,hexahydroazepin-3-yl or hexahydroazepin-4-yl group which is substitutedin the 1 position by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)aminogroup,

[0151] or an azetidin-2-yl-C₁₋₂-alkyl, azetidin-3-yl-C₁₋₂-alkyl,pyrrolidin-2-yl-C₁₋₂-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C₁₋₂-alkyl,piperidin-2-yl-C₁₋₂-alkyl, piperidin-3-yl, piperidin-3-yl-C₁ I₂-alkyl,piperidin-4-yl or piperidin-4-yl-C₁₋₂-alkyl group, while theabove-mentioned groups may each be substituted by one or two C₁₋₃-alkylgroups,

[0152] while by the aryl groups mentioned in the definition of the abovegroups are meant phenyl or naphthyl groups, which may be mono- ordisubstituted by R_(h) independently of one another, where thesubstituents are identical or different and R_(h) denotes a fluorine,chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro,amino, aminocarbonyl, aminosulphonyl, methylsulphonyl, acetylamino,methylsulphonylamino, C₁₋₃-alkyl, cyclopropyl, ethenyl, ethynyl,hydroxy, C₁₋₃-alkyloxy, difluoromethoxy or trifluoromethoxy group,

[0153] by the heteroaryl groups mentioned in the definitions of theabove-mentioned groups are meant a pyrrolyl, furanyl, thienyl, pyridyl,indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinylgroup,

[0154] or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one ortwo metbyne groups are replaced by nitrogen atoms,

[0155] or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl orisoquinolinyl group wherein one to three methyne groups are replaced bynitrogen atoms,

[0156] or a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl,2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl,1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl,1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl,1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl,2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl,2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl,1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl,1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl,3,4-dihydro-4-oxo-quinazolinyl,1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl,1,2-dihydro-2-oxoquinoxalinyl,1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl,1,2-dihydro-1-oxo-phthalazinyl,1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl,2,3-dihydro-benzo[1,4]dioxinyl or3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group,

[0157] while the above-mentioned heteroaryl groups may be substituted byR¹⁰ to R¹⁴ where R¹⁰ to R¹⁴ are as hereinbeforedefined,

[0158] and, unless otherwise stated, the above-mentioned alkyl, alkenyland alkynyl groups may be straight-chain or branched,

[0159] as well as the derivatives which are N-oxidised or methylated orethylated at the cyclic nitrogen atom in the 3 position or 9 position ofthe hypoxanthine skeleton,

[0160] as well as the derivatives wherein the 6-oxo group of thehypoxanthine skeleton is replaced by a thioxo group,

[0161] with the proviso that the compounds

[0162]8-(piperidin-4-ylmethyl)-7-(4-fluorobenzyl)-1,7-dihydro-purin-6-one and

[0163]8-(1-methyl-piperidin-4-ylmethyl)-7-(4-fluorobenzyl)-1,7-dihydro-purin-6-one

[0164] are excluded,

[0165] the tautomers, enantiomers, diastereomers, the mixtures thereof,the prodrugs thereof and the salts thereof.

[0166] Compounds which contain a group that can be cleaved in vivo areprodrugs of the corresponding compounds wherein this group that can becleaved in vivo has been cleaved.

[0167] The carboxy groups mentioned in the definition of theabove-mentioned groups may be replaced by a group which can be convertedinto a carboxy group in vivo or by a group which is negatively chargedunder physiological conditions,

[0168] and furthermore the amino and imino groups mentioned in thedefinition of the above-mentioned groups may be substituted by a groupwhich can be cleaved in vivo. Such groups are described for example inWO 98/46576 and by N. M. Nielsen et al. in International Journal ofPharmaceutics 39, 75-85 (1987).

[0169] By a group which can be converted in vivo into a carboxy group ismeant, for example, a hydroxymethyl group, a carboxy group esterifiedwith an alcohol wherein the alcohol moiety is preferably a C₁₋₆-alkanol,a phenyl-C₁₋₃-alkanol, a C₃₋₉-cycloalkanol, while a C₅₋₈-cycloalkanolmay additionally be substituted by one or two C₁₋₃-alkyl groups, aC₅₋₈-cycloalkanol wherein a methylene group in the 3 or 4 position isreplaced by an oxygen atom or by an imino group optionally substitutedby a C₁₋₃-alkyl, phenyl-C₁₋₃-alkyl, phenyl-C₁₋₃-alkyloxycarbonyl orC₂₋₆-alkanoyl group and the cycloalkanol moiety may additionally besubstituted by one or two C₁₋₃-alkyl groups, a C₄₋₇-cycloalkenol, aC₃₋₅-alkenol, a phenyl-C₃₋₅-alkenol, a C₃₋₅-alkynol orphenyl-C₃₋₅-alkynol with the proviso that no bonds to the oxygen atomstart from a carbon atom which carries a double or triple bond, aC₃₋₈-cycloalkyl-C₁₋₃-alkanol, a bicycloalkanol with a total of 8 to 10carbon atoms which may additionally be substituted in the bicycloalkylmoiety by one or two C₁₋₃-alkyl groups, a1,3-dihydro-3-oxo-1-isobenzofuranol or an alcohol of formula

R_(p)—COO—(R_(q)CR_(r))—OH,

[0170] wherein

[0171] R_(p) denotes a C₁₋₈-alkyl, C₅₋₇-cycloalkyl, C₁₋₈-alkyloxy,C₅₋₇-cycloalkyloxy, phenyl or phenyl-C₁₋₃-alkyl group,

[0172] R_(q) denotes a hydrogen atom, a C₁₋₃-alkyl, C₅₋₇-cycloalkyl orphenyl group and

[0173] R_(r) denotes a hydrogen atom or a C₁₋₃-alkyl group,

[0174] by a group which is negatively charged under physiologicalconditions is meant, for example, a tetrazol-5-yl,phenylcarbonylaminocarbonyl, trifluoromethylcarbonylaminocarbonyl,C₁₋₆-alkylsulphonylamino, phenylsulphonylamino, benzylsulphonylamino,trifluoromethylsulphonylamino, C₁₋₆-alkylsulphonylaminocarbonyl,phenylsulphonylaminocarbonyl, benzylsulphonylaminocarbonyl orperfluoro-C₁₋₆-alkylsulphonylaminocarbonyl group

[0175] and by a group which can be cleaved in vivo from an imino oramino group is meant, for example, a hydroxy group, an acyl group suchas a phenylcarbonyl group optionally mono- or disubstituted by fluorine,chlorine, bromine or iodine atoms, by C₁₋₃-alkyl or C₁₋₃-alkyloxygroups, while the substituents may be identical or different, apyridinoyl group or a C₁₋₁₆-alkanoyl group such as the formyl, acetyl,propionyl, butanoyl, pentanoyl or hexanoyl group, a3,3,3-trichloropropionyl or allyloxycarbonyl group, aC₁₋₁₆-alkyloxycarbonyl or C₁₋₁₆-alkylcarbonyloxy group, wherein hydrogenatoms may be wholly or partially replaced by fluorine or chlorine atomssuch as the methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, tert. butoxycarbonyl,pentoxycarbonyl, hexoxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl,decyloxycarbonyl, undecyloxycarbonyl, dodecyloxycarbonyl,hexadecyloxycarbonyl, methylcarbonyloxy, ethylcarbonyloxy,2,2,2-trichloro-ethylcarbonyloxy, propylcarbonyloxy,isopropylcarbonyloxy, butylcarbonyloxy, tert. butylcarbonyloxy,pentylcarbonyloxy, hexylcarbonyloxy, octylcarbonyloxy, nonylcarbonyloxy,decylcarbonyloxy, undecylcarbonyloxy, dodecylcarbonyloxy orhexadecylcarbonyloxy group, a phenyl-C₁₋₆-alkyloxycarbonyl group such asthe benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonylgroup, a 3-amino-propionyl group wherein the amino group may be mono- ordisubstituted by C₁₋₆-alkyl or C₃₋₇-cycloalkyl groups and thesubstituents may be identical or different, aC₁₋₃-alkylsulphonyl-C₂₋₄-alkyloxycarbonyl,C₁₋₃-alkyloxy-C₂₋₄-alkyloxy-C₂₋₄-alkyloxycarbonyl,R_(p)—CO—O—(P_(q)CR_(r))—O—CO, C₁₋₆-alkyl-CO—NH—(R_(s)CR_(t))—O—CO— orC₁₋₆-alkyl-CO—O—(R_(s)CR_(t))—(R_(s)CR_(t))—O—CO— group, wherein R_(p)to R_(r) are as hereinbefore defined,

[0176] R_(s) and R_(t), which may be identical or different, denotehydrogen atoms or C₁₋₃-alkyl groups.

[0177] Moreover, the saturated alkyl and alkyloxy moieties which containmore than 2 carbon atoms mentioned in the foregoing definitions andthose that follow, unless otherwise stated, also include the branchedisomers thereof such as, for example, the isopropyl, tert. butyl,isobutyl group, etc.

[0178] One sub-group deserving special mention relates to thosecompounds of general formula I wherein R¹, R² and R³ are as hereinbeforedefined and

[0179] R⁴ denotes a pyrrolidin-1-yl group which is substituted in the 3position by an amino group,

[0180] a piperidin-1-yl group which is substituted in the 3 position byan amino group,

[0181] a piperidin-3-yl or piperidin-4-yl group,

[0182] a hexahydroazepin-1-yl group which is substituted in the 3position or 4 position by an amino group,

[0183] a piperazin-1-yl or [1,4]diazepan-1-yl group,

[0184] a (2-aminocyclohexyl)amino group,

[0185] a cyclohexyl group which is substituted in the 3 position by anamino group,

[0186] or an N-(2-aminoethyl)-methylamino or anN-(2-aminoethyl)-ethylamino group,

[0187] the tautomers, enantiomers, diastereomers, the mixtures thereof,the prodrugs and the salts thereof.

[0188] Preferred compounds of the above general formula I are thosewherein

[0189] R¹ denotes a hydrogen atom,

[0190] a C₁₋₆-alkyl group,

[0191] a C₃₋₆-alkenyl group,

[0192] a C₃₋₄-alkynyl group,

[0193] a C₃₋₆-cycloalkylmethyl group,

[0194] a phenyl-C₁₋₃-alkyl group wherein the phenyl moiety issubstituted by R¹⁰ and R¹¹, where

[0195] R¹⁰ denotes a hydrogen atom, a fluorine, chlorine or bromineatom,

[0196] a methyl or trifluoromethyl group,

[0197] a cyano, aminocarbonyl, dimethylaminocarbonyl or methylsulphonylgroup,

[0198] an amino, acetylamino or methylsulphonylamino group,

[0199] a hydroxy, methoxy, difluoromethoxy, trifluoromethoxy,

[0200] carboxymethoxy, methoxycarbonylmethoxy, ethyloxycarbonylmethoxy,aminocarbonylmethoxy, methylaaminocarbonylmethoxy,ethylamino-carbonylmethoxy or dimethylaminocarbonylmethoxy group and

[0201] R¹¹ denotes a hydrogen atom, a fluorine or chlorine atom,

[0202] or a methyl or methoxy group,

[0203] a naphthylmethyl group wherein the naphthyl moiety is substitutedby R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbefore defined,

[0204] a heteroarylmethyl group where the term

[0205] heteroaryl denotes a furanyl, thienyl, oxazolyl, isoxazolyl,thiazolyl, pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl orquinazolinyl group and the above-mentioned heteroaryl groups aresubstituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbeforedefined,

[0206] a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbeforedefined,

[0207] a furanylcarbonylmethyl, thienylcarbonylmethyl orpyridylcarbonylmethyl group,

[0208] or a 2-oxo-propyl or cyclohexylcarbonylmethyl group,

[0209] R² denotes a hydrogen atom,

[0210] a C₁₋₆-alkyl group,

[0211] a C₃₋₆-alkenyl group,

[0212] a C₃₋₄-alkynyl group,

[0213] a C₃₋₆-cycloalkyl or C₃₋₆-cycloalkyl-C₁₋₃-alkyl group,

[0214] a phenyl group which is substituted by R¹⁰ and R¹¹, where R¹⁰ andR¹¹ are as hereinbefore defined,

[0215] a phenyl-C₁₋₃-alkyl group wherein the phenyl moiety issubstituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbeforedefined,

[0216] a phenyl-C₂₋₃-alkenyl group wherein the phenyl moiety issubstituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbeforedefined,

[0217] a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by R¹⁰ and R¹¹,

[0218] where R¹⁰ and R¹¹ are as hereinbefore defined,

[0219] a furanyl, thienyl or pyridyl group,

[0220] a furanyl-C₁₋₃-alkyl, thienyl-C₁₋₃-alkyl or pyridyl-C₁₋₃-alkylgroup,

[0221] a cyano group,

[0222] an amino, C₁₋₄-alkylamino or di-(C₁₋₄-alkyl)-amino group,

[0223] an amino group substituted by the groups R¹⁵ and R¹⁶ wherein

[0224] R¹⁵ denotes a hydrogen atom or a methyl or ethyl group and

[0225] R¹⁶ denotes a C₁₋₄-alkyl group which is substituted by a cyano,carboxy, methoxycarbonyl, ethyloxycarbonyl, aminocarbonyl,methylaminocarbonyl,

[0226] dimethylaminocarbonyl, ethylaminocarbonyl, diethylaminocarbonyl,pyrrolidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group,

[0227] an amino group substituted by the groups R¹⁵ and R¹⁷ wherein

[0228] R¹⁵ is as hereinbefore defined and

[0229] R¹⁷ denotes a straight-chain C₂₋₄-alkyl group which is terminallysubstituted in each case by an amino, methylamino, dimethylamino,acetylamino, ethyloxy-carbonylamino, phenylcarbonylamino,methylsulphonylamino, phenylsulphonylamino, hydroxy, methoxy, phenyloxy,methylsulphanyl or phenylsulphanyl group,

[0230] a pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-ylor 4-methyl-piperazin-1-yl group,

[0231] a C₃₋₆-cycloalkylamino or C₃₋₆-cycloalkyl-C₁₋₃-alkylamino group,

[0232] a phenylamino group,

[0233] a phenyl-C₁₋₃-alkylamino group wherein the phenyl moiety issubstituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbeforedefined,

[0234] a naphthylmethylamino group,

[0235] a heteroaryl-C₁₋₂-alkylamino group, where the term heteroaryl isas hereinbefore defined, or

[0236] a methylsulphanyl, benzylsulphanyl or (2-phenylethyl)sulphanylgroup,

[0237] R³ denotes a C₄₋₆-alkenyl group,

[0238] a C₃₋₄-alkenyl group which is substituted by a fluorine, chlorineor bromine atom or a trifluoromethyl group,

[0239] a 2-butyn-1-yl group or

[0240] a methyl group substituted by the group R_(c), where

[0241] R_(c) denotes a 1-cyclopenten-1-yl-or 1-cyclohexen-1-yl group,

[0242] a phenyl group optionally substituted by a fluorine, chlorine,bromine or iodine atom, by a methyl, trifluoromethyl, cyano, methoxy,difluoromethoxy or trifluoromethoxy group,

[0243] a phenyl group which is substituted by two fluorine atoms,

[0244] a naphthyl group or

[0245] a furanyl, thienyl, or pyridyl group, and

[0246] R⁴ denotes a piperidin-1-yl group which is substituted in the 3position by an amino group,

[0247] a hexahydroazepin-1-yl group which is substituted in the 3position or 4 position by an amino group,

[0248] a (2-aminocyclohexyl)amino group,

[0249] a cyclohexyl group which is substituted in the 3 position by anamino group, or

[0250] an N-(2-aminoethyl)-methylamino or an N-(2-aminoethyl)-ethylaminogroup,

[0251] while unless otherwise stated, the above-mentioned alkyl alkenyland alkynyl groups may be straight-chain or branched,

[0252] the tautomers, enantiomers, diastereomers, the mixtures thereofand the salts thereof.

[0253] Particularly preferred compounds of the above general formula Iare those wherein

[0254] R¹ denotes a hydrogen atom,

[0255] a methyl, benzyl or 2-phenylethyl group,

[0256] a naphthylmethyl or methoxynaphthylmethyl group or

[0257] a phenylcarbonylmethyl group,

[0258] R² denotes a hydrogen atom,

[0259] a methyl or 2-phenylethyl group,

[0260] a phenylcarbonylmethyl group,

[0261] a cyano group,

[0262] an amino, methylamino, dimethylamino, isopropylamino,cyclohexylamino- or (cyclohexylmethyl)amino group,

[0263] a benzylamino, fluorobenzylamino or (2-phenylethyl)amino group or

[0264] a piperidin-1-yl group,

[0265] R³ denotes a benzyl or 3-methyl-but-2-en-1-yl group and

[0266] R⁴ denotes a (3-amino-piperidin-1-yl) group,

[0267] the tautomers, enantiomers, diastereomers, the mixtures thereofand the salts thereof,

[0268] but particularly the compounds

[0269] (1)8-(3-amino-piperidin-1-yl)-7-benzyl-2-benzylamino-1-methyl-1,7-dihydro-purin-6-one,

[0270] (2)8-(3-amino-piperidin-1-yl)-7-benzyl-2-(4-fluoro-benzylamino)-1-methyl-1,7-dihydro-purin-6-one,

[0271] (3)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-phenylethyl)amino]-1,7-dihydro-purin-6-one,

[0272] (4)8-(3-amino-piperidin-1-yl)-7-benzyl-2-isopropylamino-1-methyl-1,7-dihydro-purin-6-one,

[0273] (5)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methylamino-1,7-dihydro-purin-6-one,

[0274] (6)8-(3-amino-piperidin-1-yl)-7-benzyl-2-cyclohexylamino-1-methyl-1,7-dihydro-purin-6-one,

[0275] (7)8-(3-amino-piperidin-1-yl)-7-benzyl-2-[(cyclohexylmethyl)amino]-1-methyl-1,7-dihydro-purin-6-one,

[0276] (8)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(piperidin-1-yl)-1,7-dihydro-purin-6-one,

[0277] (9)8-(3-amino-piperidin-1-yl)-7-benzyl-2-dimethylamino-1-methyl-1,7-dihydro-purin-6-one,

[0278] (10)2-amino-8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-1,7-dihydro-purin-6-one,

[0279] ( 11)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-methyl-but-2-en-1-yl)-1,7-dihydro-purin-6-one,

[0280] (12)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methyl-1,7-dihydro-purin-6-one,

[0281] (13)8-(3-amino-piperidin-1-yl)-1-methyl-7-(3-methyl-but-2-en-1-yl)-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one,

[0282] (14)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-1,7-dihydro-purin-6-one,

[0283] (15)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-oxo-2-phenyl-ethyl)-1,7-dihydro-purin-6-one,

[0284] (16)8-(3-amino-piperidin-1-yl)-2-methyl-7-(3-methyl-but-2-en-1-yl)-1-[(naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-one,

[0285] (17)8-(3-amino-piperidin-1-yl)-7-(3-methyl-but-2-en-1-yl)-1-[(naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-oneand

[0286] (18)8-(3-amino-piperidin-1-yl)-7-(3-methyl-but-2-en-1-yl)-1-[(4-methoxy-naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-one

[0287] as well as the tautomers, enantiomers, diastereomers, themixtures thereof and the salts thereof.

[0288] The compounds of general formula I can be prepared bydeprotecting a compound of general formula

[0289] wherein R¹, R² and R³ are as hereinbefore defined and

[0290] R⁴′ denotes one of the groups mentioned hereinbefore for R⁴ whichcontain an imino, amino or alkylamino group, while the imino, amino oralkylamino group is substituted by a protective group, optionallyfollowed by subsequent alkylation of the imino, amino or C₁₋₃-alkylaminogroup.

[0291] The liberating of an amino group from a protected precursor is astandard reaction in synthetic organic chemistry. There are manyexamples of suitable protective groups. A summary of the chemistry ofprotective groups can be found in Theodora W.Greene and Peter G. M.Wuts, Protective Groups in Organic Synthesis, Second Edition, 1991,published by John Wiley and Sons, and in Philip J. Kocienski, ProtectingGroups, published by Georg Thieme, 1994.

[0292] The following are examples of protective groups:

[0293] the tert.-butyloxycarbonyl group which can be cleaved by treatingwith an acid such as for example trifluoroacetic acid or hydrogenchloride in the presence of a solvent such as for example methylenechloride, ethyl acetate or dioxane at temperatures between 0° C. and theboiling temperature of the solvent used,

[0294] the 2,2,2-trichloroethoxycarbonyl group which can be cleaved bytreating with metals such as for example zinc or cadmium in a solventsuch as acetic acid or a mixture of tetrahydrofuran and a weak aqueousacid at temperatures between 0° C. and the boiling temperature of thesolvent used and

[0295] the carbobenzyloxycarbonyl group which can be cleaved for exampleby hydrogenolysis in the presence of a noble metal catalyst such as forexample palladium-charcoal and a solvent such as for example alcohols,ethyl acetate, dioxane, tetrahydrofuran or mixtures of these solvents attemperatures between 0° C. and the boiling point of the solvent, bytreating with boron tribromide in methylene chloride at temperaturesbetween −20° C. and ambient temperature, or by treating with aluminiumchloride/anisol at temperatures between 0° C. and ambient temperature.

[0296] The optional subsequent introduction of a C₁₋₃-alkyl group may bedone by alkylation or reductive alkylation.

[0297] The subsequent alkylation is optionally carried out in a solventor mixture of solvents such as methylene chloride, dimethylformamide,benzene, toluene, chlorobenzene, tetrahydrofuran,benzene/tetrahydrofuran or dioxane with an alkylating agent such as acorresponding halide or sulphonic acid ester, e.g. with methyl iodide,ethyl bromide, dimethyl sulphate, optionally in the presence of atertiary organic base or in the presence of an inorganic base,conveniently at temperatures between 0 and 150° C., preferably attemperatures between 0 and 100° C.

[0298] The subsequent reductive alkylation is carried out with acorresponding carbonyl compound such as formaldehyde, acetaldehyde,propionaldehyde or acetone in the presence of a complex metal hydridesuch as sodium borohydride, lithium borohydride, sodiumtriacetoxyborohydride or sodium cyanoborohydride, conveniently at a pHof 6-7 and at ambient temperature or in the presence of a hydrogenationcatalyst, e.g. with hydrogen in the presence of palladium/charcoal,under a hydrogen pressure of 1 to 5 bar. The methylation may also becarried out in the presence of formic acid as reducing agent at elevatedtemperatures, e.g. at temperatures between 60 and 120° C.

[0299] The compounds of general formula I obtained may be resolved intotheir enantiomers and/or diastereomers. Thus, for example, cis/transmixtures may be resolved into their cis and trans isomers, and compoundswith at least one optically active carbon atom may be separated intotheir enantiomers.

[0300] Thus, for example, the cis/trans mixtures may be resolved bychromatography into the cis and trans isomers thereof, the compounds ofgeneral formula I obtained which occur as racemates may be separated bymethods known per se (cf Allinger N. L. and Eliel E. L. in “Topics inStereochemistry”, Vol. 6, Wiley Interscience, 1971) into their opticalantipodes and compounds of general formula I with at least 2 asymmetriccarbon atoms may be resolved into their diastereomers on the basis oftheir physical-chemical differences using methods known per se, e.g. bychromatography and/or fractional crystallisation, and, if thesecompounds are obtained in racemic form, they may subsequently beresolved into the enantiomers as mentioned above.

[0301] The enantiomers are preferably separated by column separation onchiral phases or by recrystallisation from an optically active solventor by reacting with an optically active substance which forms salts orderivatives such as e.g. esters or amides with the racemic compound,particularly acids and the activated derivatives or alcohols thereof,and separating the diastereomeric mixture of salts or derivatives thusobtained, e.g. on the basis of their differences in solubility, whilstthe free antipodes may be released from the pure diastereomeric salts orderivatives by the action of suitable agents. Optically active acids incommon use are e.g. the D- and L-forms of tartaric acid ordibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelicacid, camphorsulphonic acid, glutamic acid, aspartic acid or quinicacid. An optically active alcohol may be for example (+) or (−)-mentholand an optically active acyl group in amides, for example, may be a(+)-or (−)-menthyloxycarbonyl.

[0302] Furthermore, the compounds of formula I obtained may be convertedinto the salts thereof, particularly for pharmaceutical use into thephysiologically acceptable salts with inorganic or organic acids. Acidswhich may be used for this purpose include for example hydrochloricacid, hydrobromic acid, sulphuric acid, methane sulphonic acid,phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid,tartaric acid or maleic acid.

[0303] Moreover, if the new compounds of formula I thus obtained containa carboxy group, they may subsequently, if desired, be converted intothe salts thereof with inorganic or organic bases, particularly forpharmaceutical use into the physiologically acceptable salts thereof.Suitable bases for this purpose include for example sodium hydroxide,potassium hydroxide, arginine, cyclohexylamine, ethanolamine,diethanolamine and triethanolamine.

[0304] The starting compounds of general formula II may be prepared bygenerally known methods and according to processes described for examplein Examples 1 to XIV.

[0305] Thus, compounds of general formula II wherein R¹, R³ and R⁴′ areas hereinbefore defined and R² denotes a hydrogen atom, may be preparedfor example by reacting a compound of formula

[0306] with a formimido-C₁₋₃-alkyl ester, optionally followed byalkylation at N-1 with a suitable alkylating agent.

[0307] Compounds of general formula II wherein R¹, R³ and R⁴′ are ashereinbefore defined and R² denotes an alkylsulphanyl, analkenylsulphanyl or alkynylsulphanyl group may be obtained for exampleby reacting compounds of general formula III with a suitableisothiocyanate and subsequently cyclising them to form compounds ofgeneral formula

[0308] followed by alkylation of the sulphur atom.

[0309] If an acyl mustard oil is used, such as for exampleethoxycarbonylisothiocyanate, first of all compounds of general formulaIV, wherein R¹ denotes a hydrogen atom are obtained, which can beconverted into the desired compounds by subsequent alkylation at thesulphur atom and at N-1.

[0310] Compounds of general formula II wherein R¹, R³ and R⁴′ are ashereinbefore defined and R² denotes an alkylsulphanyl group can beoxidised to form compounds of formula II′ wherein R²′ denotes analkylsulphinyl or an alkylsulphonyl group.

[0311] The above-mentioned compounds of general formula II′ are startingmaterials for preparing the following compounds of formula II.

[0312] Reaction with alcohols and phenols yields compounds wherein thegroup R² is linked to the purine system via an oxygen atom,

[0313] Reaction with thiols and thiophenols leads to compounds whereinR² is linked to the purine system via a sulphur atom,

[0314] Reaction with amines leads to compounds wherein R² is bound tothe purine system via a nitrogen atom and

[0315] Reaction with organometallic compounds such as for exampleGrignard reagents, alkyl- or aryl-lithium compounds or reaction withCH-acid compounds such as for example esters, nitrites or ketones leadsto compounds wherein R² is linked to the purine system via a carbonatom.

[0316] Another method of obtaining compounds of general formula IIconsists, for example, in converting compounds of general formula

[0317] wherein R¹, R² and R³ are as hereinbefore defined, into compoundsof general formula II.

[0318] For example, compounds of general formula V are converted intocompounds of general formula II wherein the group R⁴′ is bound to thepurine system via a nitrogen atom, by reacting with an orthoformate,subsequently brominating the resulting purine at C-8 and then reactingwith a corresponding amine.

[0319] For example, compounds of general formula V are converted intocompounds of general formula II wherein the group R⁴′ is bound to theC-8 atom of the purine via a C-atom by reaction with a reactivederivative of a carboxylic acid R⁴′ —COOH, where R⁴′ is as hereinbeforedefined, and subsequent cyclisation.

[0320] As already mentioned hereinbefore, the compounds of generalformula I according to the invention and the physiologically acceptablesalts thereof have valuable pharmacological properties, particularly aninhibiting effect on the enzyme DPP-IV.

[0321] The biological properties of the new compounds were investigatedas follows:

[0322] The ability of the substances and their corresponding salts toinhibit the DPP-IV activity can be demonstrated in a test set-up inwhich an extract of human colon carcinoma cell line Caco-2 is used asthe DPP IV source. The differentiation of the cells in order to inducethe DPP-IV expression was carried out as described by Reiher et al. inan article entitled “Increased expression of intestinal cell lineCaco-2”, which appeared in Proc. Natl. Acad. Sci. Vol. 90, pages5757-5761 (1993). The cell extract was obtained from cells solubilisedin a buffer (10 mM Tris HCl, 0.15 M NaCl, 0.04 t.i.u. aprotinin, 0.5%Nonidet-P40, pH 8.0) by centrifuging at 35,000 g for 30 minutes at 4° C.(to remove cell debris).

[0323] The DPP-IV assay was carried out as follows:

[0324] 50 μl substrate solution (AFC; AFC isamido-4-trifluoromethylcoumarin), final concentration 100 μM, wereplaced in black microtitre plates. 20 μl of assay buffer (finalconcentrations 50 mM Tris HCl pH 7.8, 50 mM NaCl, 1 % DMSO) was pipettedin. The reaction was started by adding 30 μl of solubilised Caco-2protein (final concentration 0.14 μg of protein per well). The testsubstances to be investigated were typically added prediluted in 20 μl,and the volume of assay buffer was then reduced accordingly. Thereaction was carried out at ambient temperature, incubating for 60minutes. Then the fluorescence was measured in a Victor 1420 MultilabelCounter, the excitation wavelength being 405 nm and the emissionwavelength being 535 nm. Blank readings (corresponding to 0 % activity)were obtained in mixtures without any Caco-2 protein (volume replaced byassay buffer), control values (corresponding to 100 % activity) wereobtained in mixtures with no substance added. The potency of the testsubstances in question, expressed as IC₅₀ values, was calculated fromdosage/activity curves consisting of 11 measuring points in each case.

[0325] The results obtained are shown in the following Table: CompoundDPP IV inhibition (Example No.) IC₅₀ (nM) 1 11 1(1) 24 1(2) 42 1(3) 1101(4) 58 1(5) 134 1(6) 48 1(7) 434 1(8) 213 1(9) 61 1(11) 54 1(12) 181(13) 152 1(14) 158 1(15) 58 1(22) 48 1(23) 157 1(24) 113 1(25) 2751(26) 40 1(27) 19 1(28) 57

[0326] The compounds prepared according to the invention are welltolerated, as for example when 30 mg/kg of the compound of Example 1were administered to rats by oral route no toxic side effects or changesin the animals' behaviour could be detected.

[0327] In view of their ability to inhibit DPP-IV activity, thecompounds of general formula I according to the invention and thecorresponding pharmaceutically acceptable salts thereof are suitable fortreating all those conditions or illnesses which can be influenced bythe inhibition of the DPP-IV activity. It is therefore to be expectedthat the compounds according to the invention will be suitable for theprevention or treatment of diseases or conditions such as type 1 andtype 2 diabetes mellitus, diabetic complications (such as e.g.retinopathy, nephropathy or neuropathies), metabolic acidosis orketosis, reactive hypoglycaemia, insulin resistance, metabolic syndrome,dyslipidaemias of various origins, arthritis, atherosclerosis andrelated diseases, obesity, allograft transplantation andcalcitonin-induced osteoporosis. In addition these substances arecapable of preventing B-cell degeneration such as e.g. apoptosis ornecrosis of pancreatic B-cells. The substances are also suitable forimproving or restoring the function of pancreatic cells and alsoincreasing the number and size of pancreatic B-cells. Additionally, andon the basis of the role of the Glucagon-Like Peptides, such as e.g.GLP-1 and GLP-2 and their link with DPP-IV inhibition, it is likely thatthe compounds according to the invention are suitable for achieving,inter alia, a sedative or anxiety-relieving effect and also offavourably affecting catabolic states after operations or hormonalstress responses or of reducing mortality or morbidity after myocardialinfarct. They. are also suitable for treating all conditions which areconnected with the above-mentioned effects and which are mediated byGLP-1 or GLP-2. The compounds according to the invention may also beused as diuretics or antihypertensives and are suitable for preventingand treating acute renal failure. Furthermore, the compounds accordingto the invention may be used to treat inflammatory diseases of therespiratory tract. They are also suitable for the prevention andtreatment of chronic inflammatory intestinal diseases such as e.g.irritable bowel syndrome (IBS), Crohn's disease or ulcerative colitisand also pancreatitis. It is also likely that they can be used for allkinds of damage to or impairment of the gastrointestinal tract such ascolitis and enteritis, for example. It is also expected that DPP-IVinhibitors and hence also the compounds according to the invention maybe used to treat infertility or to improve fertility in humans ormammals, particularly when the infertility is connected with insulinresistance or polycystic ovary syndrome. On the other hand thesesubstances are suitable for affecting sperm motility and can thus beused as male contraceptives. The substances are also suitable fortreating deficiencies of growth hormone which are associated withreduced stature, and may also be used to advantage in any indications inwhich growth hormone may be used. The compounds according to theinvention are also suitable, on the basis of their inhibitory effect onDPP IV, for treating various autoimmune diseases such as e.g. rheumatoidarthritis, multiple sclerosis, thyroiditis and Basedow's disease, etc.They may also be used to treat viral diseases and also, for example, inHIV infections, for stimulating blood production, in benign prostatichyper-plasia, gingivitis, as well as for the treatment of neuronaldefects and neurodegenerative diseases such as Alzheimer's disease, forexample. The compounds described may also be used for the treatment oftumours, particularly for modifying tumour invasion and alsometastasisation; examples here are their use in treating T-celllymphomas, acute lymphoblastic leukaemia, cell-based pancreaticcarcinomas, basal cell carcinomas or breast cancers. Other indicationsare stroke, ischaemia of various origins, Parkinson's disease andmigraine. In addition, further indications include follicular andepidermal hyperkeratoses, increased keratinocyte proliferation,psoriasis, encephalomyelitis, glomerulonephritis, lipodystrophies, aswell as psychosomatic, depressive and neuropsychiatric diseases of allkinds.

[0328] The compounds according to the invention may also be used inconjunction with other active substances. Therapeutic agents which aresuitable for such combinations include, for example, antidiabetics, suchas metformin, sulphonylureas (e.g. glibenclamid, tolbutamide,glimepiride), nateglinide, repaglinide, thiazolidinedione (e.g.rosiglitazone, pioglitazone), PPAR-gamma agonists (e.g. GI 262570) andantagonists, PPAR-gamma/alpha modulators (e.g. KRP 297),alpha-glucosidase inhibitors (e.g. acarbose, voglibose), other DPPIVinhibitors, alpha2 antagonists, insulin and insulin analogues, GLP-1 andGLP-1 analogues (e.g. exendin-4) or amylin. Also, inhibitors of proteintyrosine phosphatase 1, substances which influence deregulated glucoseproduction in the liver, such as e.g. inhibitors ofglucose-6-phosphatase, or fructose-1,6-bisphosphatase, glycogenphosphorylase, glucagon receptor antagonists and inhibitors ofphosphoenol—pyruvate carboxykinase, glycogen synthase kinase or pyruvatedehydrokinase, lipid lowering agents, such as HMG-CoA-reductaseinhibitors (e.g. simvastatin, atorvastatin), fibrates (e.g. bezafibrate,fenofibrate), nicotinic acid and its derivatives, PPAR-alpha agonists,PPAR-delta agonists, ACAT inhibitors (e.g. avasimibe) orcholesterol—resorption inhibitors such as for example ezetimibe, bileacid-binding substances such as for example cholestyramine, inhibitorsof ileac bile acid transport, HDL-raising compounds such as for exampleinhibitors of CETP or regulators of ABC 1 or active substances for thetreatment of obesity such as e.g. sibutramine or tetrahydrolipostatin,dexfenfluramine, axokine, antagonists of the cannabinoidl receptor,MCH-1 receptor antagonists, MC₄ receptor agonists, NPY5 or NPY2antagonists or β₃-agonists such as SB-418790 or AD-9677 as well asagonists of the 5HT2c receptor.

[0329] It is also possible to combine the compounds with drugs fortreating high blood pressure such as e.g. All antagonists or ACEinhibitors, diuretics, β-blockers, Ca-antagonists, etc., or combinationsthereof.

[0330] The dosage required to achieve such an effect is expediently, byintravenous route, 1 to 100 mg, preferably 1 to 30 mg, and by oral route1 to 1000 mg, preferably 1 to 100 mg, in each case 1 to 4 a day. Forthis purpose, the compounds of formula I prepared according to theinvention, optionally combined with other active substances, may beincorporated together with one or more inert conventional carriersand/or diluents, e.g. with corn starch, lactose, glucose,microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone,citric acid, tartaric acid, water, water/ethanol, water/glycerol,water/sorbitol, water/polyethylene glycol, propylene glycol,cetylstearyl alcohol, carboxymethylcellulose or fatty substances such ashard fat or suitable mixtures thereof into conventional galenicpreparations such as plain or coated tablets, capsules, powders,suspensions or suppositories.

[0331] The Examples that follow are intended to illustrate theinvention:

[0332] Preparation of the starting compounds:

EXAMPLE I

[0333] Ethyl5-Amino-3-Benzyl-2-(3-Tert.-Butyloxycarbonylamino-Piperidin-1-Yl)-3H-Imidazol-4-Carboxylate

[0334] 50 g (0.199 mol) of N-benzyl-N′-cyano-O-phenyl-isourea and 40.056g (0.2 mol) of 3-tert.-butyloxycarbonylamino-piperidine are heated to80° C. in 50 ml of dimethylformamide (DMF) for 4 hours. After standingovernight 250 ml of ethyl acetate are added, the precipitate is suctionfiltered, washed with ethyl acetate and ether and dried. More product isobtained from the mother liquor after evaporation and treatment of theresidue with ethyl acetate and ether. Total yield: 48.0 g (67.5% oftheory) of N-benzyl-N′-cyano-(3-tert.-butyloxy-carbonylamino-piperidin)-1-carboxamidine.

[0335] R_(f) value: 0.56 (aluminium oxide, methylenechloride/methanol=40: 1)

[0336] 10.008 g (28 mmol) of this substance are dissolved in 15 ml DMF.After the addition of 4.256 g (30.8 mmol) of potassium carbonate themixture is treated with ultrasound for three minutes, then 3.416 ml(30.8 mmol) of ethyl bromoacetate are added in one go and the mixture isstirred for 36 hours at ambient temperature, adding another 10 ml of DMFafter 8 hours for ease of stirring. The reaction mixture is stirred withwater, extracted with ethyl acetate, the organic phase is dried andconcentrated by evaporation. The resin obtained is purified by columnchromatography (silica gel, ethyl acetate/petroleum ether=3:l to 9: 1)

[0337] 5.4 g (43.5 % of theory) ofN-benzyl-N′-cyano-N-ethoxycarbonylmethyl-(3-tert.-butyloxy-carbonylamino-piperidin)-1-carboxamidineare obtained.

[0338] R_(f) value: 0.7 (silica gel, ethyl acetate/petroleum ether=4:1)

[0339] 5.1 g (11.498 mmol) of this compound are added batchwise to asolution of 0.785 g (11.536 mmol) of sodium ethoxide in 25 ml ofethanol. The mixture is stirred for 40 minutes at 60° C., then combinedwith 50 ml of ethanol and 10 ml of water and cooled. The precipitate issuction filtered and dissolved in methylene chloride. After drying andevaporation of the solvent, 4.8 g (94.1 % of theory) of the titlecompound is obtained.

[0340] R_(f) value: 0.4 (silica gel, ethyl acetate/petroleum ether=4: 1)

[0341] The following was obtained analogously to Example I:

[0342] (1) ethyl5-amino-3-(3-methyl-but-2-enyl)-2-(3-tert.-butyloxycarbonylamino-piperidin-1-yl)-3H-imidazol-4-carboxylate

[0343] prepared from diphenyl-N-cyanocarbonimidate, glycinethylester,(3-tert.-butyloxy-carbonylamino)-piperidine and3-methyl-but-2-en-1-yl-bromide.

[0344] R_(f) value: 0.1-0.2 (silica gel, ethyl acetate/petroleumether=1: 1)

EXAMPLE II

[0345] Tert. Butyl[1-(7-Benzyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]Carbaminate

[0346] 360 mg (0.812 mmol) of ethyl5-amino-3-benzyl-2-(3-tert.-butyloxy-carbonylamino-piperidin-1-yl)-3H-imidazol-4-carboxylateand 131.472 (1.2 mmol) of ethylformidate hydrochloride are placed in 1.3g phenol. A solution of 141.667 mg (2mmol) of sodiumethoxide in 2 ml oftetrahydrofuran (THF) is added dropwise with stirring, the THF isevaporated off and the mixture is kept for 2 hours at 150° C. The brownreaction mixture is purified through a silica gel column. 50 mg (15.7 %of theory) of the title compound were obtained.

[0347] melting point: 208° C.

[0348] R_(f) value: 0.15 (silica gel, methylene chloride/methanol=15: 1)

EXAMPLE III

[0349] Tert. Butyl[1-(7-Benzyl-1-Methyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]Carbaminate

[0350] 19 mg (0.138 mmol) of potassium carbonate and then 16 mg (0.113mmol) of methyl iodide are added to a solution of 42 mg (0.099 mmol) ofthe compound of Example II in 0.3 ml DMF. The mixture is stirred for 2hours at ambient temperature, then triturated with water and extractedwith ethyl acetate. The organic phase is washed with water and driedwith activated charcoal and magnesium sulphate. After evaporation 29 mg(66.8 % of theory) of the title compound is obtained.

[0351] R_(f) value: 0.3 (silica gel, methylene chloride/methanol=15:1)

[0352] The following was obtained analogously to Example III:

[0353] (1) tert. butyl[1-(7-benzyl-1-{2-oxo-2-phenyl-ethyl}-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0354] prepared from Example II and phenacylbromide.

[0355] R_(f) value: 0.4 (silica gel, methylene chloride/methanol=15: 1)

EXAMPLE IV

[0356] Tert. Butyl[1-(7-Benzyl-2-Methylsulphanyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]-Carbaminate

[0357] 3.186 ml (27 mmol) of ethyloxycarbonyl isothiocyanate are addeddropwise to a solution of 10.8 g (24.345 mmol) of the compound ofExample 1 in 45 ml THF. The mixture is heated to boiling for one hour,concentrated by evaporation and the residue is brought tocrystallisation by treating with diisopropylether.

[0358] 13.5 g (96.5 % of theory) of ethyl3-benzyl-2-(3-tert.-butyloxycarbonylamino-piperidin-1-yl)-5-(N′-ethyloxycarbonyl-thioureido)-3H-imidazol-4-carboxylateare obtained.

[0359] 13 g (22.620 mmol) of this compound are placed in 21 ml ofn-butanol. After the addition of 2.536 (22.6 mmol) ofpotassium-tert.-butoxide the mixture is stirred for 45 minutes at 100°C., during which time a precipitate settles out. After standingovernight at ambient temperature the mixture is combined with ether,suction filtered and dried. 10.6 g (94.7 % of theory) of tert. butyl[1-(7-benzyl-2-mercapto-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminatepotassium salt are obtained.

[0360] 10.5 g (21.225 mmol) of this compound are suspended in 25 ml ofwater, and ethanol is added to the solution. After the addition of 2.135ml (21.515 mmol) of dimethylsulphate the mixture is stirred for 4 hoursat ambient temperature. The precipitate is suction filtered, washed withcold ethanol and dried. 8.8 g (88.1 % of theory) of the title compoundare obtained.

[0361] R_(f) value: 0.3 (silica gel, methylene chloride/methanol=20:1)

[0362] The following compounds were obtained analogously to Example IV:

[0363] (1) tert. butyl[1-(7-benzyl-2-benzylsulphanyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0364] prepared from compound I, ethyloxycarbonyl isothiocyanate andbenzylbromide.

[0365] R_(f) value: 0.65 (silica gel, ethyl acetate/petroleum ether=2:1)

[0366] (2) tert. butyl[I-(7-allyl-2-methylsulphanyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0367] prepared from compound 1. 1, ethyloxycarbonyl isothiocyanate andmethyl iodide.

[0368] R_(f) value: 0.6 (silica gel, methylene chloride/methanol=10:1)

[0369] (3) tert. butyl[1-(7-benzyl-2-[2-phenylethyl]sulphanyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0370] prepared from compound I, ethyloxycarbonyl isothiocyanate and2-phenylethylbromide.

[0371] R_(f) value: 0.65 (silica gel, ethyl acetate/petroleum ether=2:1)

EXAMPLE V

[0372]Tert-Butyl[1-(7-Benzyl-1-Methyl-2-Methylsulphanyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]-Carbaminate

[0373] A suspension of 2.5 g (5.312 mmol) of compound IV in 15 ml DMF iscombined with 645.15 mg (5.75mmol) of potassium-tert.-butoxide. 922.605mg (6.5 mmol) of methyl iodide are added to the resulting solution andthe mixture is stirred overnight at ambient temperature. Water is addedand the mixture is extracted with methylene chloride. The organic phaseis washed with water, dried and concentrated by evaporation. The residueis crystallised with diisopropylether. 2 g (77.7 % of theory) of thetitle compound are obtained.

[0374] R_(f) value: 0.55 (silica gel, methylene chloride/methanol=20:1)

[0375] The following compounds were obtained analogously to Example V:

[0376] (1) tert. butyl [1-(7-benzyl-2-methylsulphanyl-1-phenacyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0377] prepared from compound IV and phenacylbromide.

[0378] R_(f) value: 0.7 (aluminium oxide, methylenechloride/methanol=40:1)

[0379] (2) tert. butyl[1-(1-methyl-7-(3-methyl-butenyl)-2-methylsulphanyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0380] prepared from compound IV.1 and methyl iodide.

[0381] R_(f) value: 0.4 (silica gel, methylene chloride/methanol=20:1)

[0382] (3) tert. butyl[1-(1-benzyl-7-benzyl-2-methylsulphanyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0383] prepared from compound IV and benzylbromide.

[0384] R_(f) value: 0.75 (silica gel, ethyl acetate/petroleum ether=4:1)

[0385] (4) tert. butyl[1-(7-benzyl-2-methylsulphanyl-1-(2-phenylethyl)-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0386] prepared from compound IV and 2-phenylethylbromide.

[0387] R_(f) value: 0.75 (silica gel, ethyl acetate/petroleum ether=4:1)

[0388] (5) tert. butyl[1-(7-benzyl-2-benzylsulphanyl-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0389] prepared from compound IV.1 and methyl iodide.

[0390] R_(f) value: 0.85 (silica gel, ethyl acetate/petroleum ether=1:2)

[0391] (6) tert. butyl[1-(7-benzyl-2-[2-phenylethyl]sulphanyl-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0392] prepared from compound IV.3 and methyl iodide.

[0393] R_(f) value: 0.65 (silica gel, ethyl acetate/petroleum ether=1:2)

EXAMPLE VI

[0394] Tert.Butyl[1-(7-Benzyl-1-Methyl-2-Methylsulphinyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]-Carbaminateand Tert. Butyl[1-(7-Benzyl-1-Methyl-2-Methylsulphonyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]-Carbaminate

[0395] A solution of 250 mg (0.516 mmol) of compound V in 5 ml ofdichloromethane and 0.5 ml of methanol is combined with 120.789 mg (0.7mmol) of m-chloro-perbenzoic acid 15 with stirring and cooling with ice.After 30 minutes the ice bath is removed and the mixture is stirredovernight at ambient temperature. 50 ml of methylene chloride are addedand the mixture is extracted with 10 % soda solution. The organic phaseis washed with water, dried and concentrated by evaporation. 220 mg ofthe two title compounds are obtained in the ratio 45:55.

[0396] R_(f) value: 0.1 (sulphoxide) and 0.8 (sulphone) (silica gel,ethyl acetate)

[0397] The following compounds were obtained analogously to Example VI:

[0398] (1) tert. butyl[1-methyl-7-(3-methyl-but-2-enyl)-2-methylsulphinyl-6-oxo-6,7-dihydro-1H-purin-8-yl]-piperidin-3-yl)-carbaminateand tert. butyl[1-methyl-7-(3-methyl-but-2-enyl)-2-methylsulphonyl-6-oxo-6,7-dihydro-1H-purin-8-yl-]-piperidin-3-yl)-carbaminate

[0399] prepared from compound V.2 and m-chloro-perbenzoic acid. Theproduct obtained after a reaction time of 80 minutes is the sulphoxide,which contains a maximum of 10% sulphone.

[0400] R_(f) value: 0.5 (silica gel, methylene chloride/methanol=10:1)

[0401] (2) tert. butyl[1-(7-benzyl-2-methanesulphonyl-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0402] prepared from compound V.

[0403] R_(f) value: 0.75 (silica gel, ethyl acetate)

[0404] Mass spectrum (ESI⁺): m/z=517 [M+H]⁺

EXAMPLE VII

[0405] Tert.Butyl[1-(7-Benzyl-2-Benzylamino-1-Methyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]-Carbaminate

[0406] 258.312 mg of the mixture obtained in Example VI and 214.313 mgof benzylamine are stirred for 16 hours at ambient temperature. Themixture is triturated with 20 ml of diisopropylether, the precipitate issuction filtered, dissolved in a little methylene chloride andcrystallised with diisopropylether. 250 mg of the title compound areobtained.

[0407] R_(f) value: 0.55 (silica gel, ethyl acetate)

[0408] The following compounds were prepared analogously to Example VII:

[0409] (1) tert. butyl[1-(7-benzyl-2-[4-fluoro-benzyl]amino-1-methyl-6-oxo-6,7-dihydro- 1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0410] prepared from Example VI and 4-fluoro-benzylamine

[0411] R_(f) value: 0.49 (silica gel, ethyl acetate)

[0412] (2) tert. butyl [1-(7-benzyl-1-methyl-2-(2-phenylethyl)amino-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0413] prepared from Example VI and 2-(2-phenylethyl)amine.

[0414] R_(f) value: 0.5 (silica gel, ethyl acetate)

[0415] (3) tert. butyl[1-(7-benzyl-2-isopropylamino-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl-]-carbaminate

[0416] prepared from Example VI and isopropylamine.

[0417] R_(f) value: 0.6 (silica gel, methylene chloride/methanol=9:1)

[0418] (4) tert. butyl[1-(7-benzyl-1-methyl-2-methylamino-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0419] prepared from Example VI and methylamine gas.

[0420] R_(f) value: 0.27 (silica gel, methylene chloride/methanol=19:1)

[0421] (5) tert. butyl[1-(7-benzyl-2-cyclohexylamino-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0422] prepared from Example VI and cyclohexylamine

[0423] R_(f) value: 0.65 (silica gel, methylene chloride/methanol=9:1)

[0424] (6) tert. butyl[1-(7-benzyl-2-cyclohexylmethylamino-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0425] prepared from Example VI and cyclohexylmethylamine.

[0426] R_(f) value: 0.54 (silica gel, ethyl acetate)

[0427] (7) tert. butyl[1-(7-benzyl-1-methyl-2-piperidino-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0428] prepared from Example VI and piperidine.

[0429] R_(f) value: 0.45 (silica gel, methylene chloride/methanol=20:1)

[0430] (8) tert. butyl[1-(7-benzyl-2-dimethylamino-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0431] prepared from Example VI and dimethylamine

[0432] R_(f) value: 0.65 (silica gel, methylene chloride/methanol=9:1)

[0433] (9) tert. butyl [1-(2-amino-7-benzyl-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0434] prepared from Example VI and arnmonia gas.

[0435] R_(f) value: 0.4 (silica gel, methylene chloride/methanol=10:1)

[0436] (10) tert. butyl[1-(2-benzylamino-1-methyl-7-[3-methylbut-2-enyl]-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidino-3-yl]-carbaminate

[0437] prepared from Example VI. 1 and benzylamine

[0438] R_(f) value: 0.6 (silica gel, ethyl acetate)

EXAMPLE VIII

[0439] Tert. Butyl[1-(7-Benzyl-1-Methyl-2-Methyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Piperidin-3-Yl]-Carbaminate

[0440] A solution of 258.32 mg of Example VI in 3 ml of THF is combinedwith 0.2 ml of a 3-molar solution of methylmagnesium bromide in etherand the mixture is stirred for 48 hours at ambient temperature. 50 ml ofether were added and the mixture was extracted with water at pH 4. Theorganic phase was dried and concentrated by evaporation. The productobtained was purified through a silica gel column. 55 mg of the titlecompound are obtained.

[0441] R_(f) value: 0.55 (silica gel, methylene chloride/methanol=10:1)

[0442] The following compound was obtained analogously to Example VIII:

[0443] (1) tert. butyl[1-(1-methyl-7-[3-methyl-but-2-enyl]-2-[2-phenylethyl]-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminate

[0444] prepared from Example VI. 1 and (2-phenylethyl)magnesium bromide.

[0445] R_(f) value: 0.5 (silica gel; methylene chloride/methanol=10:1)

EXAMPLE IX

[0446] Tert. Butyl{1-[7-Benzyl-1-Methyl-6-Oxo-2-(2-Oxo-2-Phenyl-Ethyl)-6,7-Dihydro-1H-Purin-8-Yl]-Piperidin-3-Yl}-Carbaminate

[0447] A solution of 132 mg of acetophenone in 1 ml of tetrahydrofuranis added dropwise at 0° C. to a solution of 0.63 ml of n-butyllithium(1.6 M in n-hexane) and 119 mg diisopropylamine in 2 ml oftetrahydrofuran. After 15 minutes a solution of 500 mg of tert. butyl[1-(7-benzyl-2-methanesulphonyl-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminatein 2 ml of tetrahydrofuran is added dropwise. Then the cooling bath isremoved and the reaction mixture is stirred overnight at ambienttemperature. As the thin layer chromatograph shows that there is stillsome starting material present, a further 0.94 ml of n-butyllithium (1.6M in n-hexane) are added. After another 24 hours the reaction solutionis diluted with 50 ml of water, adjusted to pH 6 with 2 N hydrochloricacid and extracted with ethyl acetate. The combined organic phases arewashed with water, dried over magnesium sulphate and evaporated down.The crude product is purified by chromatography over a silica gel columnwith methylene chloride as eluant. 54 mg of the title compound areobtained.

[0448] R_(f) value: 0.55 (aluminium oxide, methylene chloride)

[0449] Mass spectrum (ESI⁺): m/z=557 [M+H]⁺

EXAMPLE X

[0450] Tert.Butyl[1-(7-Benzyl-2-Cyano-1-Methyl-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl)-Niperidin-3-Yl]-Carbaminate

[0451] 268 mg of tetrabutylammonium cyanide are added to 258 mg of tert.butyl[1-(7-benzyl-2-methanesulphonyl-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-piperidin-3-yl]-carbaminatein 1 ml of methylene chloride and the reaction mixture is stirred fortwo days at ambient temperature. The reaction solution ischromatographed through a silica gel column with methylenechloride/methanol (97:3 to 90: 1) as eluant. Theproduct thus obtained iscrystallised from diisopropylether. 126 mg of the title compound areobtained.

[0452] R_(f) value: 0.75 (silica gel, methylene chloride/methanol=10:1)

[0453] Mass spectrum (ESI⁺): m/z=464 [M+H]⁺

EXAMPLE XI

[0454] Tert. Butyl{1-[1-Benzyl-2-Methyl-7-(3-Methyl-But-2-Enyl)-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl]-Piperidin-3-Yl}-Carbaminate

[0455] A mixture of 105 mg of tert. butyl{1-[5-methyl-i-(3-methyl-but-2-enyl)-7-oxo-1,7-dihydro-imidazo[4,5-d][1,3]oxazin-2-yl]-piperidin-3-yl}-carbaminateand 40 μl benzylamine in 1.5 ml of methylene chloride is stirred for twodays at 40° C. Then 57 μl triethylamine and 37 μl phosphorus oxychlorideare added and the reaction mixture is stirred for a further six hours at40° C. For working up the reaction mixture is combined with aqueouspotassium carbonate solution and extracted with ethyl acetate. Thecombined organic phases are dried over magnesium sulphate and evaporateddown. The crude product is purified by chromatography over a silica gelcolumn with methylene chloride/methanol (1:0 to 20:1) as eluant. 30 mgof the title compound are obtained.

[0456] Mass spectrum (ESI⁺): m/z=507 [M+H]⁺

[0457] The following is obtained analogously to Example XI:

[0458] (1) tert.butyl(1-{1-[(naphthalen-1-yl)methyl]-2-methyl-7-(3-methyl-but-2-enyl)-6-oxo-6,7-dihydro-1H-purin-8-yl}-piperidin-3-yl)-carbaminate

[0459] prepared from Example XII and 1-aminomethyl-naphthalene.

[0460] Mass spectrum (ESI⁺): m/z=557 [M+H]⁺

EXAMPLE XII

[0461] Tert. Butyl{1-[5-Methyl-1-(3-Methyl-But-2-Enyl)-7-Oxo-1,7-Dihydro-Imidazo[4,5-D][1,3]Oxazin-2-Yl]-Piperidin-3-Yl}-Carbaminate

[0462] A mixture of 1.0 g of ethyl5-acetylamino-2-(3-tert.-butyloxycarbonylamino-piperidin-1-yl)-3-(3-methyl-but-2-enyl)-3H-imidazol-4-carboxylate,566 mg of triphenylphosphine and 0.97 ml of triethylamine in 16 ml oftoluene is heated to 80° C. and combined with a solution of 702 mg of1,2-dibromo-tetrachloroethane in 8 ml of toluene. The reaction mixtureis stirred for four hours at 80° C., then the precipitate formed isfiltered off and washed with toluene. The filtrate is evaporated down invacuo and chromatographed through a silica gel column withcyclohexane/ethyl acetate as eluant. 804 mg of the title compound areobtained.

[0463] Mass spectrum (ESI⁺): m/z=418 [M+H]⁺

[0464] The following compound is obtained from Example XIII. 1 under thesame reaction conditions:

[0465] (1) ethyl 2-(3-tert.-butyloxycarbonylamino-piperidin-1-yl)-5-isocyano-3-(3-methyl-but-2-enyl)-3H-imidazol-4-carboxylate

[0466] Mass spectrum (ESI⁺): m/z=432 [M+H]⁺

EXAMPLE XIII

[0467] Ethyl5-Acetylamino-2-(3-Tert.-Butyloxycarbonylamino-Piperidin-1-Yl)-3-(3-Methyl-But-2-Enyl)-3H-Imidazol-4-Carboxylate

[0468] prepared from Example I.1 by reaction with acetylchloride in thepresence of pyridine in methylene chloride.

[0469] Mass spectrum (ESI⁺): m/z=464 [M+H]⁺

[0470] The following compound is obtained analogously to Example XIII:

[0471] (1) ethyl2-(3-tert.-butyloxycarbonylamino-piperidin-1-yl)-5-formylamino-3-(3-methyl-but-2-enyl)-3H-imidazol-4-carboxylate

[0472] prepared from Example I.1 by reaction with formic acid and aceticanhydride in the presence of pyridine in methylene chloride.

[0473] Mass spectrum (ESI⁺): m/z=450 [M+H]⁺

EXAMPLE XIV

[0474] Tert. Butyl(1-{1-[(Naphthalen-1-Yl)Methyl]-7-(3-Methyl-But-2-Enyl)-6-Oxo-6,7-Dihydro-1H-Purin-8-Yl}-Piperidin-3-Yl)-Carbaminate

[0475] 210 mg of 1-aminomethyl-naphthalene and 30 mg of copper(I)oxideare added to 295 mg of ethyl2-(3-tert.-butyloxycarbonylamino-piperidin-1-yl)-5-isocyano-3-(3-methyl-but-2-enyl)-3H-imidazol-4-carboxylatein 7 ml of toluene. The reaction mixture is stirred for 10 hours at 120°C. After cooling to ambient temperature it is diluted with ethyl acetateand filtered through Celite. The filtrate is combined with water andextracted with ethyl acetate. The combined extracts are dried overmagnesium sulphate and evaporated down. The crude product ischromatographed through a silica gel column with methylenechloride/methanol (1:0 to 10:1) as eluant. 306 mg of the title compoundare obtained, contaminated with ethyl5-amino-2-(3-tert.-butoxycarbonylamino-piperidin-1-yl)-3-(3-methyl-but-2-enyl)-3H-imidazol-4-carboxylate.

[0476] Mass spectrum (ESI⁺): m/z=543 [M+H]⁺

[0477] The following compound is obtained analogously to Example XIV:

[0478] (1) tert. butyl(1-{1-[(4-methoxy-naphthalen-1-yl)methyl]-7-(3-methyl-but-2-enyl)-6-oxo-6,7-dihydro-1H-purin-8-yl}-piperidin′-3-yl)-carbaminate

[0479] prepared from Example XII.1 and1-aminomethyl-4-methoxy-naphthalene.

[0480] R_(f) value: 0.17 (silica gel, cyclohexane/ethyl acetate=1:9)

[0481] Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

[0482] Examples of the preparation of the end products:

EXAMPLE 1

[0483]8-(3-Amino-Piperidin-1-Yl)-7-Benzyl-2-Benzylamino-1-Methyl-1.7-Dihydro-Purin-6-One

[0484] A solution of 200 mg of Example VII in 2 ml of dichloromethane iscombined with 3 ml of trifluoroacetic acid with stirring and coolingwith ice. After 30 minutes the ice bath is removed and stirring iscontinued for 2 hours. The solvent is evaporated at low temperature, theresidue is triturated with ether, suction filtered and dried in vacuo.150 mg (73.1 % of theory) of the trifluoroacetate of the title compoundare obtained.

[0485] R_(f) value: 0.45 (aluminium oxide, methylenechloride/methanol=20:1)

[0486]¹H—NMR spectrum (400 MHz, DMSO-d₆):

[0487] 1.5 (m,2H), 1,7 (m,1H), 1.95 (m,1H), 2.8 (m,1H), 3.0 (m,1H), 3.15(d,1H), 3.4 (s+m,4H), 3.5(d,IH), 4.55 (d,2H), 5.35(s,2H), 7.1-7.5(m,12H), 8.0 (s,3H), 8.1-8.3 (m,1H)

[0488] The following compounds were obtained analogously to Example 1:

[0489] (1)8-(3-amino-piperidin-1-yl)-7-benzyl-2-(4-fluoro-benzylamino)-1-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0490] prepared from Example VII.1 and trifluoroacetic acid

[0491] R_(f) value: 0.69 (aluminium oxide, methylenechloride/methanol=9: 1)

[0492] (2)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-phenylethyl)amino]-1,7-dihydro-purin-6-onetrifluoroacetate

[0493] prepared from Example VII.2 and trifluoroacetic acid.

[0494] R_(f) value: 0.75 (aluminium oxide, methylenechloride/methanol=9:1)

[0495] (3)8-(3-amino-piperidin-1-yl)-7-benzyl-2-isopropylamino-1-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0496] prepared from Example VII.3 and trifluoroacetic acid.

[0497] R_(f) value: 0.68 (aluminium oxide, methylenechloride/methanol=9:1)

[0498] (4)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methylamino-1,7-dihydro-purin-6-onetrifluoroacetate

[0499] prepared from Example VII.4 and trifluoroacetic acid.

[0500] R_(f) value: 0.26 (aluminium oxide, methylenechloride/methanol=9:1)

[0501] (5)8-(3-amino-piperidin-1-yl)-7-benzyl-2-cyclohexylamino-1-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0502] prepared from Example VII.5 and trifluoroacetic acid.

[0503] R_(f) value: 0.65 (aluminium oxide, methylenechloride/methanol=9:1)

[0504] (6)8-(3-amino-piperidin-1-yl)-7-benzyl-2-cyclohexylmethylamino-1-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0505] prepared from Example VII.6 and trifluoroacetic acid.

[0506] R_(f) value: 0.69 (aluminium oxide, methylenechloride/methanol=9:1)

[0507] (7)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(piperidin-1-yl)-1,7-dihydro-purin-6-one hydrochloride

[0508] prepared from Example VII.7 and hydrogen chloride in dioxane.

[0509] R_(f) value: 0.3-0.5 (aluminium oxide, methylenechloride/methanol=20:1)

[0510] (8) 8-(3-amino-piperidin-1-yl)-7-benzyl-2-dimethylamino-1-methyl-1,7-dihydro-purin-6-one trifluoroacetate

[0511] prepared from Example VII.8 and trifluoroacetic acid.

[0512] R_(f) value: 0.69 (aluminium oxide, methylenechloride/methanol=9:1)

[0513] (9)2-amino-8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0514] prepared from Example VII.9 and trifluoroacetic acid.

[0515] R_(f) value: 0.2 (aluminium oxide, methylenechloride/methanol=10:1)

[0516] (10)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-methyl-but-2-en-1-yl)-1,7-dihydro-purin-6-onetrifluoroacetate

[0517] prepared from Example VII.10 and trifluoroacetic acid.

[0518] R_(f) value: 0.55 (aluminium oxide, methylenechloride/methanol=IO: 1)

[0519] (11)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0520] prepared from Example VIII and trifluoroacetic acid.

[0521] R_(f) value: 0.6 (aluminium oxide, methylenechloride/methanol=10:1)

[0522] (12)8-(3-amino-piperidin-1-yl)-1-methyl-7-(3-methyl-but-2-en-1-yl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-onetrifluoroacetate

[0523] prepared from Example VIII.1 and trifluoroacetic acid.

[0524] R_(f) value: 0.4 (aluminium oxide, methylenechloride/methanol=20:1)

[0525] (13)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-1,7-dihydro-purin-6-onehydrochloride

[0526] prepared from Example III and hydrogen chloride in dioxane.

[0527] R_(f) value: 0.2-0.5 (aluminium oxide, methylenechloride/methanol=20: 1)

[0528] (14)8-(3-amino-piperidin-1-yl)-7-benzyl-2-methylsulphanyl-1,7-dihydro-purin-6-onehydrochloride

[0529] prepared from Example IV and hydrogen chloride in dioxane.

[0530] R_(f) value: 0.5 (aluminium oxide, methylenechloride/methanol=10:1)

[0531] (15)8-(3-amino-piperidin-1-yl)-7-benzyl-2-benzylsulphanyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0532] prepared from Example IV.1 and trifluoroacetic acid.

[0533] R_(f) value: 0.5-0.6 (aluminium oxide, methylenechloride/methanol=10:1)

[0534] (16)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methylsulphanyl-1,7-dihydro-purin-6-onehydrochloride

[0535] prepared from Example V and hydrogen chloride in dioxane.

[0536] R_(f) value: 0.5 (aluminium oxide, methylenechloride/methanol=20: 1)

[0537] (17)8-(3-amino-piperidin-1-yl)-7-benzyl-2-methylsulphanyl-1-(2-phenyl-2-oxo-ethyl)-1,7-dihydro-purin-6-onehydrochloride

[0538] prepared from Example V.1 and hydrogen chloride in dioxane.

[0539] R_(f) value: 0.4 (aluminium oxide, methylenechloride/methanol=20:1)

[0540] (18)8-(3-amino-piperidin-1-yl)-1-benzyl-7-benzyl-2-methylsulphanyl-1,7-dihydro-purin-6-onehydrochloride

[0541] prepared from Example V.3 and hydrogen chloride.

[0542] R_(f) value: 0.4-0.5 (aluminium oxide, methylenechloride/methanol=20:1)

[0543] (19)8-(3-amino-piperidin-1-yl)-7-benzyl-2-methylsulphanyl-1-(2-phenylethyl)-1,7-dihydro-purin-6-onehydrochloride

[0544] prepared from Example V.4 and hydrogen chloride.

[0545] R_(f) value: 0.4 (aluminium oxide, methylenechloride/methanol=20: 1)

[0546] (20)8-(3-amino-piperidin-1-yl)-7-benzyl-2-benzylsulphanyl-1-methyl-1,7-dihydro-purin-6-one

[0547] prepared from Example V.5 and hydrogen chloride.

[0548] R_(f) value: 0.5 (aluminium oxide, methylenechloride/methanol=20: 1)

[0549] (21)8-(3-amino-piperidin-1-yl)-7-benzyl-2-[(2-phenylethyl)sulphanyl]-1-methyl-1,7-dihydro-purin-6-one

[0550] prepared from Example V.6 and hydrogen chloride.

[0551] R_(f) value: 0.55 (aluminium oxide, methylenechloride/methanol=20:1)

[0552] (22)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-oxo-2-phenyl-ethyl)-I,7-dihydro-purin-6-one trifluoroacetate

[0553] prepared from Example III.1 and trifluoroacetic acid.

[0554] R_(f) value: 0.65 (aluminium oxide, methylenechloride/methanol=10:1)

[0555] (23)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-oxo-2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0556] prepared from Example IX and trifluoroacetic acid.

[0557] R_(f) value: 0.20 (silica gel, methylene chloride/methanol=10:1)

[0558] Mass spectrum (ESI⁺): m/z=457 [M+H]⁺

[0559] (24)8-(3-amino-piperidin-1-yl)-7-benzyl-2-cyano-1-methyl-1,7-dihydro-purin-6-onetrifluoroacetate

[0560] prepared from Example X and trifluoroacetic acid.

[0561] R_(f) value: 0.50 (aluminium oxide, methylenechloride/methanol=20: 1)

[0562] Mass spectrum (ESI⁺): m/z=364 [M+H]⁺

[0563] (25)8-(3-amino-piperidin-1-yl)-1-benzyl-2-methyl-7-(3-methyl-but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0564] prepared from Example XI and trifluoroacetic acid.

[0565] Mass spectrum (ESI⁺): m/z=407 [M+H]⁺

[0566] (26)8-(3-amino-piperidin-1-yl)-2-methyl-7-(3-methyl-but-2-en-1-yl)-1-[(naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-one

[0567] prepared from Example XI.1 and trifluoroacetic acid.

[0568] Mass spectrum (ESI⁺): m/z=457 [M+H]⁺

[0569] (27)8-(3-amino-piperidin-1-yl)-7-(3-methyl-but-2-en-1-yl)-1-[(naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-one

[0570] prepared from Example XIV and trifluoroacetic acid.

[0571] Mass spectrum (ESI⁺): m/z=443 [M+H]⁺

[0572] (28)8-(3-amino-piperidin-1-yl)-7-(3-methyl-but-2-en-1-yl)-1-[(4-methoxy-naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-one

[0573] prepared from Example XV.1 and trifluoroacetic acid.

[0574] Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

[0575] The following compounds may also be obtained analogously to thepreceding Examples and other methods known from the literature:

[0576] (1)8-(3-amino-piperidin-1-yl)-7-benzyl-1-ethyl-2-benzylamino-1,7-dihydro-purin-6-one

[0577] (2)8-(3-amino-piperidin-1-yl)-7-benzyl-1-propyl-2-benzylamino-1,7-dihydro-purin-6-one

[0578] (3)8-(3-amino-piperidin-1-yl)-7-benzyl-1-isopropyl-2-benzylamino-1,7-dihydro-purin-6-one

[0579] (4)8-(3-amino-piperidin-1-yl)-7-benzyl-1-butyl-2-benzylamino-1,7-dihydro-purin-6-one

[0580] (5)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-methyl-propyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0581] (6)8-(3-amino-piperidin-1-yl)-7-benzyl-1-pentyl-2-benzylamino-1,7-dihydro-purin-6-one

[0582] (7)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-methyl-butyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0583] (8)8-(3-amino-piperidin-1-yl)-7-benzyl-1-hexyl-2-benzylamino-1,7-dihydro-purin-6-one

[0584] (9)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4-methyl-pentyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0585] (10)8-(3-amino-piperidin-1-yl)-7-benzyl-1-allyl-2-benzylamino-1,7-dihydro-purin-6-one

[0586] (11)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-methyl-but-2-en-1-yl)-2-benzylamino-1,7-dihydro-purin-6-one

[0587] (12)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(prop-2-in-1-yl)-2-benzylamino-1,7-dihydro-purin-6-one

[0588] (13)8-(3-amino-piperidin-1-yl)-7-benzyl-1-cyclopropylmethyl-2-benzylamino-1,7-dihydro-purin-6-one

[0589] (14)8-(3-amino-piperidin-1-yl)-7-benzyl-1-cyclohexylmethyl-2-benzylamino-1,7-dihydro-purin-6-one

[0590] (15)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4-chlorobenzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0591] (16)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-fluorobenzyl)-2-benzylaamino-1,7-dihydro-purin-6-one

[0592] (17)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4-methylbenzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0593] (18) 8-(3-amino-piperidin-1-yl)-7-benzyl- l-(2,4-dimethylbenzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0594] (19)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2,4-dimethoxybenzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0595] (20)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-trifluoromethyl-benzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0596] (21)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-trifluoromethoxy-benzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0597] (22)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-difluoromethoxy-benzyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0598] (23)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(furan-2-yl-methyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0599] (24)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(thien-2-yl-methyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0600] (25)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-methyl-isoxazol-5-yl-methyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0601] (26)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(pyridin-4-yl-methyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0602] (27) 8-(3-amino-piperidin-1-yl)-7-benzyl- l-[2-(4-methyl-phenyl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0603] (28)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2,4-dichloro-phenyl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0604] (29)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0605] (30)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-trifluoromethyl-phenyl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0606] (31)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-trifluoromethoxy-phenyl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0607] (32)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-difluoromethoxy-phenyl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0608] (33)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(furan-2-yl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0609] (34)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(thien-2-yl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0610] (35)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(pyridin-3-yl)-2-oxo-ethyl]-2-benzylamino-1,7-dihydro-purin-6-one

[0611] (36)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-oxopropyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0612] (37)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-cyclohexyl-2-oxo-ethyl)-2-benzylamino-1,7-dihydro-purin-6-one

[0613] (38)8-(3-amino-piperidin-1-yl)-7-benzyl-1-ethyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0614] (39)8-(3-amino-piperidin-1-yl)-7-benzyl-1-propyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0615] (40)8-(3-amino-piperidin-1-yl)-7-benzyl-1-isopropyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0616] (41)8-(3-amino-piperidin-1-yl)-7-benzyl-1-butyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0617] (42)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-methyl-propyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0618] (43)8-(3-amino-piperidin-1-yl)-7-benzyl-1-pentyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0619] (44) 8-(3-amino-piperidin-1-yl)-7-benzyl- l-(3-methyl-butyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0620] (45)8-(3-amino-piperidin-1-yl)-7-benzyl-1-hexyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0621] (46)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4-methyl-pentyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0622] (47)8-(3-amino-piperidin-1-yl)-7-benzyl-1-allyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0623] (48)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-methyl-but-2-en-1-yl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0624] (49)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(prop-2-in-1-yl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0625] (50)8-(3-amino-piperidin-1-yl)-7-benzyl-1-cyclopropylmethyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0626] (51)8-(3-amino-piperidin-1-yl)-7-benzyl-1-cyclohexylmethyl-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0627] (52)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4-chlorobenzyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0628] (53)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-fluorobenzyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0629] (54)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4-methylbenzyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0630] (55)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2,4-dimethylbenzyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0631] (56)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2,4-dimethoxybenzyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0632] (57)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-trifluoromethyl-benzyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0633] (58)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-trifluoromethoxy-benzyl)-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0634] (59)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-difluoromethoxy-benzyl)-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0635] (60)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(furan-2-yl-methyl)-2-(2-phenylethyl)-7-dihydro-purin-6-one

[0636] (61)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(thien-2-yl-methyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0637] (62)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(3-methyl-isoxazol-5-yl-methyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0638] (63)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(pyridin-4-yl-methyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0639] (64)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-methyl-phenyl)-2-oxo-ethyl]-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0640] (65)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2,4-dichloro-phenyl)-2-oxo-ethyl]-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0641] (66)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0642] (67)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-trifluoromethyl-phenyl)-2-oxo-ethyl]-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0643] (68)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-trifluoromethoxy-phenyl)-2-oxo-ethyl]-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0644] (69)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(4-difluoromethoxy-phenyl)-2-oxo-ethyl]-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0645] (70)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(furan-2-yl)-2-oxo-ethyl]-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0646] (71)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(thien-2-yl)-2-oxo-ethyl]-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0647] (72)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(pyridin-3-yl)-2-oxo-ethyl]-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0648] (73)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-oxo-propyl)-2-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0649] (74)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-cyclohexyl-2-oxo-ethyl)-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one

[0650] (75)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-ethylamino-1,7-dihydro-purin-6-one

[0651] (76)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-propylamino-1,7-dihydro-purin-6-one

[0652] (77)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-butylamino-1,7-dihydro-purin-6-one

[0653] (78)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-methyl-propylamino)-1,7-dihydro-purin-6-one

[0654] (79)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(N-ethyl-N-methyl-amino)-1,7-dihydro-purin-6-one

[0655] (80)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-diethylamino-1,7-dihydro-purin-6-one

[0656] (81)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(N-methyl-N-propyl-amino)-1,7-dihydro-purin-6-one

[0657] (82)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(N-butyl-N-methyl-amino)-1,7-dihydro-purin-6-one

[0658] (83)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-hydroxyethyl-amino)-1,7-dihydro-purin-6-one

[0659] (84)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[N-methyl-N-(2-hydroxyethyl)-amino]-1,7-dihydro-purin-6-one

[0660] (85)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-methoxy-ethylamino)-1,7-dihydro-purin-6-one

[0661] (86)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-methoxy-propylamino)-1,7-dihydro-purin-6-one

[0662] (87)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[N-methyl-N-(2-methoxy-ethyl)-amino]-1,7-dihydro-purin-6-one

[0663] (88)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-phenoxyethyl)-amino]-1,7-dihydro-purin-6-one

[0664] (89)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-aminoethyl)-amino]-1,7-dihydro-purin-6-one

[0665] (90)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(3-aminopropyl)-amino]-1,7-dihydro-purin-6-one

[0666] (91)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-methylamino-ethyl)-amino]-1,7-dihydro-purin-6-one

[0667] (92)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(3-dimethylamino-propyl)amino]-1,7-dihydro-purin-6-one

[0668] (93)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-acetylamino-ethyl)amino]-1,7-dihydro-purin-6-one

[0669] (94)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-benzoylamino-ethyl)amino]-1,7-dihydro-purin-6-one

[0670] (95)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-ethoxycarbonylamino-ethyl)amino]-1,7-dihydro-purin-6-one

[0671] (96)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-methylsulphanyl-ethyl)amino]-1,7-dihydro-purin-6-one

[0672] (97)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-phenylsulphanyl-ethyl)amino]-1,7-dihydro-purin-6-one

[0673] (98)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-cyano-ethyl)amino]-1,7-dihydro-purin-6-one

[0674] (99)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(carboxymethyl)amino]-1,7-dihydro-purin-6-one

[0675] (100)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(ethoxycarbonylmethyl)amino]-1,7-dihydro-purin-6-one

[0676] (101)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(aminocarbonylmethyl)amino]-1,7-dihydro-purin-6-one

[0677] (102)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(ethylaminocarbonylmethyl)-amino]-1,7-dihydro-purin-6-one

[0678] (103)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(dimethylaminocarbonylmethyl)-amino]-1,7-dihydro-purin-6-one

[0679] (104)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(pyrrolidin-1-yl-carbonylmethyl)-amino]-1,7-dihydro-purin-6-one

[0680] (105)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(piperidin-1-yl-carbonyl-methyl)amino]-1,7-dihydro-purin-6-one

[0681] (106)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(morpholin-4-ylcarbonylmethyl)amino]-1,7-dihydro-purin-6-one

[0682] (107)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(cyclopentylmethyl)amino]-1,7-dihydro-purin-6-one

[0683] (108)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(cyclobutylmethyl)amino]-1,7-dihydro-purin-6-one

[0684] (109)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(cyclopropylmethyl)amino]-1,7-dihydro-purin-6-one

[0685] (110)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-cyclohexyl-ethyl)amino]-1,7-dihydro-purin-6-one

[0686] (111)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(3-cyclohexyl-propyl)amino]-1,7-dihydro-purin-6-one

[0687] (112)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(cyclobutylamino)-1,7-dihydro-purin-6-one

[0688] (113)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(cyclopentylamino)-1,7-dihydro-purin-6-one

[0689] (114)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(phenylamino)-1,7-dihydro-purin-6-one

[0690] (115)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3,4-dichlorobenzyl-amino)-1,7-dihydro-purin-6-one

[0691] (116)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-methylbenzyl-amino)-1,7-dihydro-purin-6-one

[0692] (117)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-methoxybenzyl-amino)-1,7-dihydro-purin-6-one

[0693] (118)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-trifluoromethylbenzyl-amino)-1,7-dihydro-purin-6-one

[0694] (119)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-trifluoromethoxybenzyl-amino)-1,7-dihydro-purin-6-one

[0695] (120)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-difluoromethoxybenzyl-amino)-1,7-dihydro-purin-6-one

[0696] (121)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3,4-methylenedioxybenzyl-amino)-1,7-dihydro-purin-6-one

[0697] (122)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(furan-2-yl-methyl)amino]-1,7-dihydro-purin-6-one

[0698] (123)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(thien-2-yl-methyl)amino]-1,7-dihydro-purin-6-one

[0699] (124)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(pyridine-2-yl-methyl)amino]-1,7-dihydro-purin-6-one

[0700] (125)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(4-methylthiazol-2-ylmethyl)-amino]-1,7-dihydro-purin-6-one

[0701] (126)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-{[2-(pyridine-2-yl)ethyl]amino}-1,7-dihydro-purin-6-one

[0702] (127)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(pyrrolidin-1-yl)-1,7-dihydro-purin-6-one

[0703] (128)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(morpholin-4-yl)-1,7-dihydro-purin-6-one

[0704] (129)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(piperazin-1-yl)-1,7-dihydro-purin-6-one

[0705] (130)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-methyl-piperazin-1-yl)-1,7-dihydro-purin-6-one

[0706] (131)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-ethyl-1,7-dihydro-purin-6-one

[0707] (132)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-propyl-1,7-dihydro-purin-6-one

[0708] (133)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-isopropyl-1,7-dihydro-purin-6-one

[0709] (134) 8-(3-amino-piperidin-1-yl)-7-benzyl- l-methyl-2-butyl-1,7-dihydro-purin-6-one

[0710] (135)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-methyl-propyl)-1,7-dihydro-purin-6-one

[0711] (136)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-pentyl-1,7-dihydro-purin-6-one

[0712] (137)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-methyl-butyl)-1,7-dihydro-purin-6-one

[0713] (138)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-hexyl-1,7-dihydro-purin-6-one

[0714] (139)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-methyl-pentyl)-1,7-dihydro-purin-6-one

[0715] (140)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-allyl-1,7-dihydro-purin-6-one

[0716] (141)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-methyl-but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0717] (142)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(hex-5-en-1-yl)-1,7-dihydro-purin-6-one

[0718] (143)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(pent-4-en-1-yl)-1,7-dihydro-purin-6-one

[0719] (144)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(prop-2-yn-1-yl)-1,7-dihydro-purin-6-one

[0720] (145)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-phenylethenyl)-1,7-dihydro-purin-6-one

[0721] (146)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(4-methyl-phenyl)ethenyl]-1,7-dihydro-purin-6-one

[0722] (147)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-chloro-phenyl)ethenyl]-1,7-dihydro-purin-6-one

[0723] (148)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3-fluoro-phenyl)ethenyl]-1,7-dihydro-purin-6-one

[0724] (149)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3,4-dimethoxy-phenyl)-ethenyl]-1,7-dihydro-purin-6-one

[0725] (150)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3-chloro-phenyl)ethenyl]-1,7-dihydro-purin-6-one

[0726] (151)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3-trifluoromethyl-phenyl)-ethenyl]-1,7-dihydro-purin-6-one

[0727] (152)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3-trifluoromethoxy-phenyl)-ethenyl]-1,7-dihydro-purin-6-one

[0728] (153)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-phenyl-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0729] (154)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-benzyl-1,7-dihydro-purin-6-one

[0730] (155)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-phenyl-1,7-dihydro-purin-6-one

[0731] (156)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-phenyl-propyl)-1,7-dihydro-purin-6-one

[0732] (157)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(4-fluoro-benzyl)-1,7-dihydro-purin-6-one

[0733] (158)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-trifluoromethyl-benzyl)-1,7-dihydro-purin-6-one

[0734] (159)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-chloro-benzyl)-1,7-dihydro-purin-6-one

[0735] (160)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-bromo-benzyl)-1,7-dihydro-purin-6-one

[0736] (161)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-trifluoromethoxy-benzyl)-1,7-dihydro-purin-6-one

[0737] (162)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(3-methoxy-benzyl)-1,7-dihydro-purin-6-one

[0738] (163)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3-chloro-phenyl)ethyl]-1,7-dihydro-purin-6-one

[0739] (164)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-fluoro-phenyl)ethyl]-1,7-dihydro-purin-6-one

[0740] (165)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(4-methyl-phenyl)ethyl]-1,7-dihydro-purin-6-one

[0741] (166)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(4-fluoro-phenyl)ethyl]-1,7-dihydro-purin-6-one

[0742] (167)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(3-trifluoromethyl-phenyl)-ethyl]-1,7-dihydro-purin-6-one

[0743] (168)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-cyclopentyl-1,7-dihydro-purin-6-one

[0744] (169)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-cyclohexyl-1,7-dihydro-purin-6-one

[0745] (170)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(cyclohexylmethyl)-1,7-dihydro-purin-6-one

[0746] (171)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(cyclopentylmethyl)-1,7-dihydro-purin-6-one

[0747] (172)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(2-cyclohexyl-ethyl)-1,7-dihydro-purin-6-one

[0748] (173)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(furan-2-yl)-1,7-dihydro-purin-6-one

[0749] (174)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(thien-2-yl)-1,7-dihydro-purin-6-one

[0750] (175)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(pyridin-2-yl)-1,7-dihydro-purin-6-one

[0751] (176)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(pyridin-4-yl)-1,7-dihydro-purin-6-one

[0752] (177)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(furan-2-yl-methyl)-1,7-dihydro-purin-6-one

[0753] (178)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(thien-2-yl-methyl)-1,7-dihydro-purin-6-one

[0754] (179)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(pyridin-2-yl-methyl)-1,7-dihydro-purin-6-one

[0755] (180)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(furan-2-yl)ethyl]-1,7-dihydro-purin-6-one

[0756] (181)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(pyridin-2-yl)ethyl]-1,7-dihydro-purin-6-one

[0757] (182)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[3-(furan-2-yl)propyl]-1,7-dihydro-purin-6-one

[0758] (183)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[3-(pyridin-2-yl)propyl]-1,7-dihydro-purin-6-one

[0759] (184)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-chloro-but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0760] (185) 8-(3-amino-piperidin-1-yl)-2-benzylamino- l-methyl-7-(3-chloro-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0761] (186) 8-(3-amino-piperidin-1-yl)-2-benzylamino- l-methyl-7-(3-trifluoromethyl-3-chloro-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0762] (187)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3,3-dichloro-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0763] (188)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(but-2-yn-1-yl)-1,7-dihydro-purin-6-one

[0764] (189)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(cyclohexyl-1-en-1-yl-methyl)-1,7-dihydro-purin-6-one

[0765] (190)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(cyclohexylmethyl)-1,7-dihydro-purin-6-one

[0766] (191)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(4-fluoro-benzyl)-1,7-dihydro-purin-6-one

[0767] (192)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(2-chloro-benzyl)-1,7-dihydro-purin-6-one

[0768] (193)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-bromo-benzyl)-1,7-dihydro-purin-6-one

[0769] (194)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-methyl-benzyl)-1,7-dihydro-purin-6-one

[0770] (195)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-trifluoromethyl-benzyl)-1,7-dihydro-purin-6-one

[0771] (196)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(2-cyano-benzyl)-1,7-dihydro-purin-6-one

[0772] (197)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(2-methoxy-benzyl)-1,7-dihydro-purin-6-one

[0773] (198)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-trifluoromethoxy-benzyl)-1,7-dihydro-purin-6-one

[0774] (199)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-difluoromethoxy-benzyl)-1,7-dihydro-purin-6-one

[0775] (200)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3,4-difluoro-benzyl)-1,7-dihydro-purin-6-one

[0776] (201)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(naphth-1-yl-methyl)-1,7-dihydro-purin-6-one

[0777] (202)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(furan-2-yl-methyl)-1,7-dihydro-purin-6-one

[0778] (203)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(thien-2-yl-methyl)-1,7-dihydro-purin-6-one

[0779] (204)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(pyridin-2-yl-methyl)-1,7-dihydro-purin-6-one

[0780] (205)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-chloro-but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0781] (206)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-chloro-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0782] (207)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-trifluoromethyl-3-chloro-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0783] (208)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3,3-dichloro-prop-2-en-1-yl)-1,7-dihydro-purin-6-one

[0784] (209)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(but-2-yn-1-yl)-1,7-dihydro-purin-6-one

[0785] (210)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(cyclohexyl-1-en-1-yl-methyl)-1,7-dihydro-purin-6-one

[0786] (211)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(cyclohexylmethyl)-1,7-dihydro-purin-6-one

[0787] (212)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(4-fluoro-benzyl)-1,7-dihydro-purin-6-one

[0788] (213)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(2-chloro-benzyl)-1,7-dihydro-purin-6-one

[0789] (214)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-bromo-benzyl)-1,7-dihydro-purin-6-one

[0790] (215)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-methyl-benzyl)-1,7-dihydro-purin-6-one

[0791] (216)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-trifluoromethyl-benzyl)-1,7-dihydro-purin-6-one

[0792] (217)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(2-cyano-benzyl)-1,7-dihydro-purin-6-one

[0793] (218)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(2-methoxy-benzyl)-1,7-dihydro-purin-6-one

[0794] (219)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-trifluoromethoxy-benzyl)-1,7-dihydro-purin-6-one

[0795] (220)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3-difluoromethoxy-benzyl)-1,7-dihydro-purin-6-one

[0796] (221)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(3,4-difluoro-benzyl)-1,7-dihydro-purin-6-one

[0797] (222)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(naphth-1-yl-methyl)-1,7-dihydro-purin-6-one

[0798] (223)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(fiuran-2-yl-methyl)-1,7-dihydro-purin-6-one

[0799] (224)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(thien-2-yl-methyl)-1,7-dihydro-purin-6-one

[0800] (225)8-(3-amino-piperidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-(pyridin-2-yl-methyl)-1,7-dihydro-purin-6-one

[0801] (226)8-(3-amino-piperidin-1-yl)-2-(²-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0802] (227)8-(3-amino-pyrrolidin-1-yl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0803] (228)8-(piperidin-3-yl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0804] (229)8-(piperidin-4-yl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0805] (230)8-(3-amino-hexahydroazepin-1-yl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0806] (231)8-(4-amino-hexahydroazepin-1-yl)-2-benzylaamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0807] (232)8-(piperazin-1-yl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0808] (233)8-(I,4-diazepan-1-yl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0809] (234)8-(2-amino-cyclohexylamino)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0810] (235)8-(3-amino-cyclohexyl)-2-benzylamino-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0811] (236)8-(3-amino-pyrrolidin-1-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0812] (237)8-(piperidin-3-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0813] (238)8-(piperidin-4-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0814] (239)8-(3-amino-hexahydroazepin-1-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0815] (240)8-(4-amino-hexahydroazepin-1-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0816] (241)8-(piperazin-1-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0817] (242)8-(1,4-diazepan-1-yl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0818] (243)8-(2-amino-cyclohexylamino)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0819] (244)8-(3-amino-cyclohexyl)-2-(2-phenylethyl)-1-methyl-7-benzyl-1,7-dihydro-purin-6-one

[0820] (245)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0821] (246)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(2-methyl-but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0822] (247)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(2,3-dimethyl-but-2-en-1-yl)-1,7-dihydro-purin-6-one

[0823] (248)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(cyclopent-1-en-1-yl-methyl)-1,7-dihydro-purin-6-one

[0824] (249)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-phenyl-2-oxo-ethyl)-1,7-dihydro-purin-6-one

[0825] (250)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2-amino-phenyl)-2-oxo-ethyl]-1,7-dihydro-purin-6-one

[0826] (251)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-l,7-dihydro-purin-6-one

[0827] (252)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2-methylsulphonylamino-phenyl)-2-oxo-ethyl]-1,7-dihydro-purin-6-one

[0828] (253)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-1,7-dihydro-purin-6-one

[0829] (254)8-(3-amino-piperidin-1-yl)-7-benzyl-1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-1,7-dihydro-purin-6-one

[0830] (255)8-(3-amino-piperidin-1-yl)-7-benzyl-1-{2-[2-(ethoxycarbonylmethoxy)-phenyl]-2-oxo-ethyl}-1,7-dihydro-purin-6-one

[0831] (256)8-(3-amino-piperidin-1-yl)-7-benzyl-1-{2-[2-(aminocarbonylmethoxy)-phenyl]-2-oxo-ethyl}-1,7-dihydro-purin-6-one

[0832] (257)8-(3-amino-piperidin-1-yl)-7-benzyl-1-{2-[2-(methylaminocarbonyl-methoxy)-phenyl]-2-oxo-ethyl}-1,7-dihydro-purin-6-one

[0833] (258)8-(3-amino-piperidin-1-yl)-7-benzyl-1-{2-[2-(ethylaminocarbonyl-methoxy)-phenyl]-2-oxo-ethyl}-1,7-dihydro-purin-6-one

[0834] (259)8-(3-amino-piperidin-1-yl)-7-benzyl-1-{2-[2-(dimethylaminocarbonyl-methoxy)-phenyl]-2-oxo-ethyl}-1,7-dihydro-purin-6-one

[0835] (260)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(naphth-1-yl-methyl)-1,7-dihydro-purin-6-one

[0836] (261)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(isoquinolin-1-yl-methyl)-1,7-dihydro-purin-6-one

[0837] (262)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(quinazolin-2-yl-methyl)-1,7-dihydro-purin-6-one

[0838] (263)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(quinolin-4-yl-methyl)-I,7-dihydro-purin-6-one

[0839] (264)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(quinazolin-4-yl-methyl)-1,7-dihydro-purin-6-one

[0840] (265)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-phenylethyl)-1,7-dihydro-purin-6-one

[0841] (266)8-[(2-aminoethyl)amino]-7-benzyl-1-methyl-2-benzylamino-1,7-dihydro-purin-6-one

[0842] (267)8-[N-methyl-N-(2-aminoethyl)-amino]-7-benzyl-1-methyl-2-benzylamino-1,7-dihydro-purin-6-one

[0843] (268)8-[N-ethyl-N-(2-aminoethyl)-amino]-7-benzyl-1-methyl-2-benzylamino-1,7-dihydro-purin-6-one

[0844] (269)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-cyanophenyl)ethyl]-1,7-dihydro-purin-6-one

[0845] (270)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-aminocarbonyl-phenyl)-ethyl]-1,7-dihydro-purin-6-one

[0846] (271)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-dimethylaminocarbonyl-phenyl)ethyl]-1,7-dihydro-purin-6-one

[0847] (272)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-methylsulphonyl-phenyl)-ethyl]-1,7-dihydro-purin-6-one

[0848] (273)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[2-(2-methylsulphonylamino-phenyl)ethyl]-1,7-dihydro-purin-6-one

[0849] (274)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-methylsulphonylamino-ethyl)-amino]-1,7-dihydro-purin-6-one

[0850] (275)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-phenylsulphonylamino-ethyl)-amino]-1,7-dihydro-purin-6-one

[0851] (276)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(naphth-1-yl-methyl)amino]-1,7-dihydro-purin-6-one

[0852] (277)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(quinazolin-2-yl-methyl)amino]-1,7-dihydro-purin-6-one

[0853] (278)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(isoquinolin-1-yl-methyl)amino]-1,7-dihydro-purin-6-one

[0854] (279)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4,5-dimethyl-oxazol-2-yl-methyl)-1,7-dihydro-purin-6-one

[0855] (280)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4,5-dimethyl-thiazol-2-yl-methyl)-1,7-dihydro-purin-6-one

[0856] (281)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(4,6-dimethyl-pyrimidin-2-yl-methyl)-1,7-dihydro-purin-6-one

[0857] (282)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(pyrazin-2-yl-methyl)-1,7-dihydro-purin-6-one

[0858] (283)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(3-methyl-isoxazol-5-yl-methyl)-amino]-1,7-dihydro-purin-6-one

[0859] (284)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(4,5-dimethyl-oxazol-2-yl-methyl)-amino]-1,7-dihydro-purin-6-one

[0860] (285)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(pyrazin-2-yl-methyl)-amino]-1,7-dihydro-purin-6-one

EXAMPLE 2

[0861] Coated Tablets Containing 75 mg of Active Substance

[0862] 1 Tablet Core Contains: active substance 75.0 mg calciumphosphate 93.0 mg corn starch 35.5 mg polyvinylpyrrolidone 10.0 mghydroxypropylmethylcellulose 15.0 mg magnesium stearate 1.5 mg 230.0 mg

[0863] Preparation:

[0864] The active substance is mixed with calcium phosphate, cornstarch, polyvinylpyrrolidone, hydroxypropylmethylcellulose and half thespecified amount of magnesium stearate. Blanks 13 mm in diameter areproduced in a tablet-making machine and these are then rubbed through ascreen with a mesh size of 1.5 mm using a suitable machine and mixedwith the rest of the magnesium stearate. This granulate is compressed ina tablet-making machine to form tablets of the desired shape.

[0865] Weight of core: 230 mg

[0866] die: 9 mm, convex

[0867] The tablet cores thus produced are coated with a film consistingessentially of hydroxypropylmethylcellulose. The finished film-coatedtablets are polished with beeswax.

[0868] Weight of coated tablet: 245 mg.

EXAMPLE 3

[0869] Tablets Containing 100 mg of Active Substance

[0870] Composition: 1 tablet contains: active substance 100.0 mg lactose80.0 mg corn starch 34.0 mg polyvinylpyrrolidone 4.0 mg magnesiumstearate 2.0 mg 220.0 mg

[0871] Method of Preparation:

[0872] The active substance, lactose and starch are mixed together anduniformly moistened with an aqueous solution of thepolyvinylpyrrolidone. After the moist composition has been screened (2.0mm mesh size) and dried in a rack-type drier at 50° C. it is screenedagain (1.5 mm mesh size) and the lubricant is added. The finishedmixture is compressed to form tablets.

[0873] Weight of tablet: 220 mg

[0874] Diameter: 10 mm, biplanar, faceted on both sides and notched onone side.

EXAMPLE 4

[0875] Tablets Containing 150 mg of Active Substance

[0876] Composition: 1 tablet contains: active substance 150.0 mgpowdered lactose 89.0 mg corn starch 40.0 mg colloidal silica 10.0 mgpolyvinylpyrrolidone 10.0 mg magnesium stearate 1.0 mg 300.0 mg

[0877] Preparation:

[0878] The active substance mixed with lactose, corn starch and silicais moistened with a 20% aqueous polyvinylpyrrolidone solution and passedthrough a screen with a mesh size of 1.5 mm. The granules, dried at 45°C., are passed through the same screen again and mixed with thespecified amount of magnesium stearate. Tablets are pressed from themixture.

[0879] Weight of tablet: 300 mg

[0880] die: 10 mm, flat

EXAMPLE 5

[0881] Hard Gelatine Capsules Containing 150 mg of Active Substance

[0882] 1 Capsule Contains: active substance 150.0 mg corn starch (dried)approx. 80.0 mg lactose (powderedapprox. 87.0 mg magnesium stearate 3.0mg approx. 420.0 mg

[0883] Preparation:

[0884] The active substance is mixed with the excipients, passed througha screen with a mesh size of 0.75 mm and homogeneously mixed using asuitable apparatus. The finished mixture is packed into size 1 hardgelatine capsules.

[0885] Capsule filling: approx. 320 mg

[0886] Capsule shell: size 1 hard gelatine capsule.

EXAMPLE 6

[0887] Suppositories Containing 150 mg of Active Substance

[0888] 1 Suppository Contains: active substance 150.0 mgpolyethyleneglycol 1500 550.0 mg polyethyleneglycol 6000 460.0 mgpolyoxyethylene sorbitan monostearate 840.0 mg 2,000.0 mg

[0889] Preparation:

[0890] After the suppository mass has been melted the active substanceis homogeneously distributed therein and the melt is poured into chilledmoulds.

EXAMPLE 7

[0891] Suspension Containing 50 mg of Active Substance

[0892] 100 ml of Suspension Contain: active substance 1.00 gcarboxymethylcellulose-Na-salt 0.10 g methyl p-hydroxybenzoate 0.05 gpropyl p-hydroxybenzoate 0.01 g glucose 10.00 g glycerol 5.00 g 70%sorbitol solution 20.00 g flavouring 0.30 g dist. water     ad 100 ml

[0893] Preparation:

[0894] The distilled water is heated to 70° C. The methyl and propylp-hydroxybenzoates together with the glycerol and sodium salt ofcarboxymethylcellulose are dissolved therein with stirring. The solutionis cooled to ambient temperature and the active substance is added andhomogeneously dispersed therein with stirring. After the sugar, thesorbitol solution and the flavouring have been added and dissolved, thesuspension is evacuated with stirring to eliminate air.

[0895] 5 ml of suspension contain 50 mg of active substance.

EXAMPLE 8

[0896] Amnoules Containing 10 mg Active Substance

[0897] Composition: active substance 10.0 mg 0.01 N hydrochloric acidq.s. double-distilled water  ad  2.0 ml

[0898] Preparation:

[0899] The active substance is dissolved in the necessary amount of 0.01N HCl, made isotonic with common salt, filtered sterile and transferredinto 2 ml ampoules.

EXAMPLE 9

[0900] Ampoules Containing 50 mg of Active Substance

[0901] Composition: active substance 50.0 mg 0.01 N hydrochloric acidq.s. double-distilled water  ad 10.0 ml

[0902] Preparation:

[0903] The active substance is dissolved in the necessary amount of 0.01N HCl, made isotonic with common salt, filtered sterile and transferredinto 10 ml ampoules.

1. A compound of the formula (I):

wherein R¹ denotes a hydrogen atom, a C₁₋₈-alkyl group, a C₃₋₈-alkenylgroup, a C₃₋₄-alkenyl group which is substituted by aC₁₋₂-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a C₃₋₈-alkynylgroup, a C₁₋₆-alkyl group substituted by a group R_(a), where R_(a)denotes a C₃₋₇-cycloalkyl, heteroaryl, cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl,4-methylpiperazin-1-ylcarbonyl or 4-ethylpiperazin-1-ylcarbonyl group, aC₁₋₆-alkyl group substituted by a phenyl group, where the phenyl ring issubstituted by the groups R¹⁰ to R¹⁴ and R¹⁰ denotes a hydrogen atom, afluorine, chlorine, bromine or iodine atom, a C₁₋₄-alkyl, hydroxy orC₁₋₄-alkyloxy group, a nitro, amino, C₁₋₃-alkylamino,di-(C₁₋₃-alkyl)-amino, cyan-C₁₋₃-alkylamino,N-(cyan-C₁₋₃-alkyl)-N-(C₁₋₃-alkyl)-amino,C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkylamino, pyrrolidin-1-yl, piperidin-1-yl,morpholin-4-yl, piperazin-1-yl or 4-(C₁₋₃-alkyl)-piperazin-1-yl group, aformylamino, C₁₋₃-alkyl-carbonylamino, C₃₋₆-cycloalkyl-carbonylamino,C₃₋₆-cycloalkyl-C₁₋₃-alkyl-carbonylamino, arylcarbonylamino,aryl-C₁₋₃-alkyl-carbonyl-amino, C₁₋₃-alkyloxy-carbonylamino,aminocarbonylamino, C₁₋₃-alkyl-amino-carbonylaamino,di-(C₁₋₃-alkyl)-aminocarbonylamino, pyrrolidin-1-yl-carbonylamino,piperidin-1-yl-carbonylamino, morpholin-4-yl-carbonylamino,piperazin-1-yl-carbonylamino or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonylamino, C₁₋₃-alkyl-sulphonylamino,bis-(C₁₋₃-alkylsulphonyl)-amino, aminosulphonylamino,C₁₋₃-alkyl-amino-sulphonylamino, di-(C₁₋₃-alkyl)-amino-sulphonyl amino,pyrrolidin-1-yl-sulphonylamino, piperidin-1-yl-sulphonylamino,morpholin-4-yl-sulphonylamino, piperazin-1-yl-sulphonylaamino or 4-(C 1₃-alkyl)-piperazin-1-yl-sulphonylamino,(C₁₋₃-alkylamino)-thiocarbonylamino,(C₁₋₃-alkyloxy-carbonylamino)-carbonylamino, arylsulphonylamino oraryl-C₁₋₃-alkyl-sulphonylamino group, an N-(C₁₋₃-alkyl)-formylamino,N-(C₁₋₃-alkyl)-N-(C₁₋₃-alkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(C₃₋₆-cycloalkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(C₃₋₆-cycloalkyl-C₁₋₃-alkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(arylcarbonyl)-amino,N-(C₁₋₃-alkyl)-N-(aryl-C₁₋₃-alkyl-carbonyl)-amino,N-(C₁₋₃-alkyl)-N-(C₁₋₃-alkyloxy-carbonyl)-amino,N-(aminocarbonyl)-N-(C₁₋₃-alkyl)-amino,N-(C₁₋₃-alkyl-aminocarbonyl)-N-(C₁₋₃-alkyl)-amino,N-[di-(C₁₋₃-alkyl)aminocarbonyl]-N-(C₁₋₃-alkyl)-amino,N-(C₁-3-alkyl)-N-(C₁₋₃-alkyl-sulphonyl)-amino,N-(C₁₋₃-alkyl)-N-(arylsulphonyl)-amino orN-(C₁₋₃-alkyl)-N-(aryl-C₁₋₃-alkyl-sulphonyl)-amino group, a2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl,2,5-dioxo-imidazolidin-1-yl or 2-oxo-hexahydropyrimidin-1-yl groupwherein the nitrogen atom in the 3 position may be substituted in eachcase by a methyl or ethyl group, a cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkyl-aminocarbonyl, di-(C 1₃-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl,piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl,piperazin-1-yl-carbonyl or 4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl group,a C₁₋₃-alkyl-carbonyl or an arylcarbonyl group, a carboxy-C₁₋₃-alkyl,C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl, cyano-C₁₋₃-alkyl,aminocarbonyl-C₁₋₃-alkyl, C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyl,di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyl,pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyl, piperidin-1-yl-carbonyl-C₁₋₃-alkyl,morpholin-4-yl-carbonyl-C₁₋₃-alkyl, piperazin-1-yl-carbonyl-C₁₋₃-alkylor 4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyl group, acarboxy-C₁₋₃-alkyloxy, C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyloxy,cyano-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy,C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyloxy,di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy,pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyloxy,piperidin-1-yl-carbonyl-C₁₋₃-alkyloxy,morpholin-4-yl-carbonyl-C₁₋₃-alkyloxy,piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy group, ahydroxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl,pyrrolidin-1-yl-C₁₋₃-alkyl, piperidin-1-yl-C₁₋₃-alkyl,morpholin-4-yl-C₁₋₃-alkyl, piperazin-1-yl-C₁₋₃-alkyl,4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyl group, a hydroxy-C₁₋₃-alkyloxy,C₁₋₃-alkyloxy-C₁₋₃-alkyloxy, C₁₋₃-alkylsulphanyl-C₁-3-alkyloxy,C₁₋₃-alkylsulphinyl-C₁₋₃-alkyloxy, C₁₋₃-alkylsulphonyl-C₁₋₃-alkyloxy,amino-C₁₋₃-alkyloxy, C₁₋₃-alkylamino-C₁₋₃-alkyloxy,di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyloxy, pyrrolidin-1-yl-C₁₋₃-alkyloxy,piperidin-1-yl-C₁₋₃-alkyloxy, morpholin-4-yl-C₁₋₃-alkyloxy,piperazin-1-yl-Cf ₃-alkyloxy,4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyloxy group, a mercapto,C₁₋₃-alkylsulphanyl, C₁₋₃-alkysulphinyl, C₁₋₃-alkylsulphonyl,C₁₋₃-alkylsulphonyloxy, arylsulphonyloxy, trifluoromethylsulphanyl,trifluoromethylsulphinyl or trifluoromethylsulphonyl group, a sulpho,aminosulphonyl, C₁₋₃-alkyl-aminosulphonyl,di-(C₁₋₃-alkyl)-amino-sulphonyl, pyrrolidin-1-yl-sulphonyl,piperidin-1-yl-sulphonyl, morpholin-4-yl-sulphonyl,piperazin-1-yl-sulphonyl or 4-(C₁₋₃-alkyl)-piperazin-1-yl-sulphonylgroup, a methyl or methoxy group substituted by 1 to 3 fluorine atoms,an ethyl or ethyloxy group substituted by 1 to 5 fluorine atoms, aC₂₋₄-alkenyl or C₂₋₄-alkynyl group, a C₃₋₄-alkenyloxy or C₃₋₄-alkynyloxygroup, a C₃₋₆-cycloalkyl or C₃₋₆-cycloalkyloxy group, aC₃₋₆-cycloalkyl-C₁₋₃-alkyl or C₃₋₆-cycloalkyl-C₁₋₃-alkyloxy group or anaryl, aryloxy, aryl-C₁₋₃-alkyl or aryl-C₁₋₃-alkyloxy group, R¹¹ and R¹²,which may be identical or different, in each case represent a hydrogenatom, a fluorine, chlorine, bromine or iodine atom, a C₁₋₃-alkyl,trifluoromethyl, hydroxy, C₁₋₃-alkyloxy or cyano group, or R¹¹ togetherwith R¹², if they are bound to adjacent carbon atoms, also represent amethylenedioxy, difluoromethylenedioxy or a straight-chain C₃₋₅-alkylenegroup and R¹³ and R¹⁴, which may be identical or different, in each caserepresent a hydrogen atom, a fluorine, chlorine or bromine atom, atrifluoromethyl, C₁₋₃-alkyl or C₁₋₃-alkyloxy group, a phenyl-C₁₋₄-alkylgroup wherein the alkyl moiety is substituted by a cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkyl-aminocarbonyl,di-(C₁₋₃-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl,piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl-group and the phenylmoiety is substituted by the groups R¹⁰ to R¹⁴, while R¹⁰ to R¹⁴ are ashereinbefore defined, a phenyl group substituted by the groups R¹⁰ toR¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, a phenyl-C₂₋₃-alkenylgroup wherein the phenyl moiety is substituted by the groups R¹⁰ to R¹⁴,where R¹⁰ to R¹⁴ are as hereinbefore defined, aphenyl-(CH₂)_(m)—A—(CH₂)_(n)—group wherein the phenyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore definedand A represents a carbonyl group, m represents the number 0, 1 or 2 andn represents the number 1, 2 or 3, a phenylcarbonylmethyl group whereinthe phenyl moiety is substituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are ashereinbefore defined and the methyl moiety is substituted by aC₁₋₃-alkyl group, a phenyl-(CH₂)_(m)—B—(CH₂)_(n)—group wherein thephenyl moiety is substituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, m and nare as hereinbefore defined and B denotes a methylene group which issubstituted by a hydroxy, C₁₋₃-alkyloxy, amino, C₁₋₃-alkylamino,di-(C₁₋₃-alkyl)-amino, mercapto, C₁₋₃-alkylsulphanyl,C₁₋₃-alkylsulphinyl or C₁₋₃-alkylsulphonyl group and is optionallyadditionally substituted by a methyl or ethyl group, anaphthyl-C₁₋₃-alkyl group wherein the naphthyl moiety is substituted bythe groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, anaphthyl-(CH₂)_(m)—A—(CH₂)_(n)—group wherein the naphthyl moiety issubstituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, A, m and n are ashereinbefore defined, a naphthyl-(CH₂)_(m)—B—(CH₂)_(n)—group wherein thenaphthyl moiety is substituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, B, m andn are as hereinbefore defined, a [1,4]naphthoquinon-2-yl,chromen-4-on-3-yl, 1-oxoindan-2-yl, 1,3-dioxoindan-2-yl or2,3-dihydro-3-oxo-benzofuran-2-yl group, aheteroaryl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and n are ashereinbefore defined, a heteroaryl-(CH₂)_(m)—B—(CH₂)_(n) group where B,m and n are as hereinbefore defined, a C₁₋₆-alkyl-A—(CH₂)_(n) groupwhere A and n are as hereinbefore defined, aC₃₋₇-cycloalkyl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and n are ashereinbefore defined, a C₃₋₇-cycloalkyl-(CH₂)_(m)—B—(CH₂)_(n) groupwhere B, m and n are as hereinbefore defined, an R²¹-A—(CH₂)_(n)—groupwherein R²¹ denotes a C₁₋₃-alkyloxycarbonyl, aminocarbonyl,C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)aminocarbonyl,pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl ormorpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl,4-methylpiperazin-1-yl-carbonyl or 4-ethylpiperazin-1-yl-carbonyl groupand A and n are as hereinbefore defined, a phenyl-(CH₂)_(m)—D—C₁₋₃-alkylgroup wherein the phenyl moiety is substituted by the groups R¹⁰ to R¹⁴,where R¹⁰ to R¹⁴ and m are as mentioned hereinbefore and D denotes anoxygen or sulphur atom, an imino, C₁₋₃-alkylimino, sulphinyl orsulphonyl group, a naphthyl-(CH₂)_(m)—D—C₁₋₃-alkyl group wherein thenaphthyl moiety is substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴, D and m are as mentioned hereinbefore, a C₂₋₆-alkyl groupsubstituted by a group R_(b), where R_(b) is isolated from the cyclicnitrogen atom in the 1 position of the purine skeleton by at least twocarbon atoms and R_(b) denotes a hydroxy, C₁₋₃-alkyloxy, mercapto,C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, amino,C₁₋₃-alkyl-carbonylamino, C₃₋₆-cycloalkyl-carbonyl-amino,arylcarbonylamino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino,pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-(C₁₋₃-alkyl)-piperazin-1-yl group, a C₃₋₆-cycloalkyl group, or anamino or arylcarbonylamino group, R² denotes a hydrogen atom, aC₁₋₈-alkyl group, a C₃₋₈-alkenyl group, a C₃₋₄-alkenyl group which issubstituted by a C₁₋₂-alkyloxy-carbonyl, aminocarbonyl,C₁₋₃-alkylamino-carbonyl, di-(C₁₋₃-alkyl)-amino-carbonyl,pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl ormorpholin-4-ylcarbonyl group, a C₃₋₈-alkynyl group, a C₃₋₆-cycloalkylgroup, a C₁₋₆-alkyl group substituted by a group R_(a), where R_(a) isas hereinbefore defined, a phenyl group which is substituted by R¹⁰ toR¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, a C₁₋₆-alkyl groupsubstituted by a phenyl group, wherein the phenyl ring is substituted bythe groups R¹⁰ to R¹⁴ and R¹⁰ to R¹⁴ are as hereinbefore defined, aphenyl-C₁₋₄-alkyl group wherein the alkyl moiety is substituted by acyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,C₁₋₃-alkyl-aminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl,morpholin-4-yl-carbonyl group and the phenyl moiety is substituted bythe groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, apheny1-C₂₋₃-alkenyl group wherein the phenyl moiety is substituted byR¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, a heteroarylgroup, a phenyl-(CH₂)_(m)—A or phenyl-(CH₂)_(m)—A—(CH₂)_(n) groupwherein the phenyl moiety is substituted in each case by R¹⁰ to R¹⁴,while A, R¹⁰ to R¹⁴, m and n are as hereinbefore defined, aphenylcarbonylmethyl group wherein the phenyl moiety is substituted byR¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined and the methylmoiety is substituted by a C₁₋₃-alkyl group, a phenyl-(CH₂)_(m)—B orphenyl-(CH₂)_(m)—B—(CH₂)_(n) group wherein the phenyl moiety issubstituted in each case by R¹⁰ to R¹⁴, while B, R¹⁰ to R¹⁴, m and n areas hereinbefore defined, a naphthyl-C₁₋₃-alkyl group wherein thenaphthyl moiety is substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴ are as hereinbefore defined, a naphthyl-(CH₂)_(m)—A ornaphthyl-(CH₂)_(m)—A—(CH₂)_(n) group wherein the naphthyl moiety issubstituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, A, m and n areas hereinbefore defined, a naphthyl-(CH₂)_(m)—B ornaphthyl-(CH₂)_(m)—B—(CH₂)_(n) group wherein the naphthyl moiety issubstituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, B, m and n areas hereinbefore defined, a heteroaryl-(CH₂)_(m)—A orheteroaryl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and n are ashereinbefore defined, a heteroaryl-(CH₂)_(m)—B orheteroaryl-(CH₂)_(m)—B—(CH₂)_(n) group where B, m and n are ashereinbefore defined, a C₁₋₆-alkyl-A or C₁₋₆-alkyl-A—(CH₂)_(n) groupwhere A and n are as hereinbefore defined, a C₃₋₇-cycloalkyl-(CH₂)_(m)—Aor C₃₋₇-cycloalkyl-(CH₂)_(m)—A—(CH₂)_(n) group where A, m and n are ashereinbefore defined, a C₃₋₇-cycloalkyl-(CH₂)_(m)—B orC₃₋₇-cycloalkyl-(CH₂)_(m)—B—(CH₂)_(n) group where B, m and n are ashereinbefore defined, an R²¹-A—(CH₂)_(n) group wherein R²¹, A and n areas hereinbefore defined, a phenyl-(CH₂)_(m)—D—C₁₋₃-alkyl group whereinthe phenyl moiety is substituted by the groups R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴, D and m are as mentioned hereinbefore, anaphthyl-(CH₂)_(m)—D—C₁₋₃-alkyl group wherein the naphthyl moiety issubstituted by the groups R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴, D and m are asmentioned hereinbefore, a C₁₋₆-alkyl group substituted by a group R_(b),where R_(b) is as hereinbefore defined, a cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl,4-methylpiperazin-1-ylcarbonyl or 4-ethylpiperazin-1-ylcarbonyl group,an amino, C₁₋₆-alkylamino or di-(C₁₋₆-alkyl)-amino group, an amino groupsubstituted by the groups R¹⁵ and R¹⁶ wherein R¹⁵ denotes a hydrogenatom or a C₁₋₆-alkyl group and R¹⁶ denotes a C₁₋₆-alkyl group which issubstituted by R_(a), where R_(a) is as hereinbefore defined, an aminogroup substituted by the groups R¹⁵ and R¹⁷ wherein R¹⁵ is ashereinbefore defined and R¹⁷ denotes a C₂₋₆-alkyl group which issubstituted by a hydroxy, C₁₋₃-alkyloxy, aryloxy, mercapto,C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl,C₁₋₃-alkylsulphonylamino, arylsulphanyl, arylsulphinyl, arylsulphonyl,arylsulphonylamino, C₁₋₃-alkyl-carbonylamino,C₃₋₆-cycloalkyl-carbonylamino, arylcarbonylamino,C₁₋₃-alkyl-oxycarbonylamino, aminocarbonylamino,C₁₋₃-alkyl-aminocarbonylamino, di-(C₁₋₃-alkyl)-aminocarbonylamino,amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, pyrrolidin-1-yl,piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-(C₁₋₃-alkyl)-piperazin-1-yl group, a C₃₋₆-cycloalkylamino orN-(C₃₋₆-cycloalkyl)-N-(C₁₋₃-alkyl)-amino group, a phenylamino orN-(phenyl)-N-(C₁₋₃-alkyl)-amino group wherein the phenyl moiety issubstituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are ashereinbefore defined, a phenyl-C₁₋₆-alkylamino orN-(phenyl-C₁₋₆-alkyl)-N-(C₁₋₃-alkyl)-amino group wherein the phenylmoiety is substituted in each case by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ areas hereinbefore defined, a naphthylamino orN-(naphthyl)-N-(C₁₋₃-alkyl)-amino group, a naphthyl-C₁₋₆-alkylamino orN-(naphthyl-C₁₋₆-alkyl)-N-(C₁₋₃-alkyl)-amino group, a heteroarylamino orN-(heteroaryl)-N-(C₁₋₃-alkyl)-amino group, a pyrrolidin-1-yl,piperidin-1-yl, homopiperidin-1-yl, morpholin-4-yl, homomorpholin-4-yl,piperazin-1-yl, 4-(C₁₋₃-alkyl)-piperazin-1-yl, homopiperazin-1-yl or4-(C₁₋₃-alkyl)-homopiperazin-1-yl group, or a C₁₋₆-alkyloxy, C_(3.)₆-cycloalkyloxy or C₃₋₆-cycloalkyl-C₁₋₆-alkyloxy group, aC₁₋₆-alkylsulphanyl, C₃₋₆-cycloalkylsulphanyl orC₃₋₆-cycloalkyl-C₁₋₆-alkylsulphanyl group, a phenyloxy orphenylsulphanyl group wherein the phenyl moiety is substituted in eachcase by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, aphenyl-C₁₋₆-alkyloxy or phenyl-C₁₋₆-alkylsulphanyl group wherein thephenyl moiety is substituted in each case by R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴ are as hereinbefore defined, a naphthyloxy or a naphthylsulphanylgroup wherein the naphthyl moiety is substituted in each case by R¹⁰ toR¹⁴, where R¹⁰ to R¹⁴ are as hereinbefore defined, anaphthyl-C₁₋₆-alkyloxy or naphthyl-C₁₋₆-alkylsulphanyl group wherein thenaphthyl moiety is substituted in each case by R¹⁰ to R¹⁴, where R¹⁰ toR¹⁴ are as hereinbefore defined, a heteroaryloxy or heteroarylsulphanylgroup or a heteroaryl-C₁₋₆-alkyloxy or heteroaryl-C₁₋₆-alkylsulphanylgroup, R³ denotes a C₁₋₈-alkyl group, a C₁₋₄-alkyl group substituted bythe group R_(c), where R_(c) denotes a C₃₋₇-cycloalkyl group optionallysubstituted by one or two C₁₋₃-alkyl groups, a C₅₋₇-cycloalkenyl groupoptionally substituted by one or two C₁₋₃-alkyl groups, an aryl group ora furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, while theabove-mentioned heterocyclic groups may each be substituted by one ortwo C₁₋₃-alkyl groups or by a fluorine, chlorine, bromine or iodine atomor by a trifluoromethyl, cyano or C₁₋₃-alkyloxy group, a C₃₋₈-alkenylgroup, a C₃₋₆-alkenyl group substituted by a fluorine, chlorine orbromine atom or a trifluoromethyl group, a C₃₋₈-alkynyl group, an arylgroup or an aryl-C₂₋₄-alkenyl group, and R⁴ denotes an azetidin-1-yl orpyrrolidin-1-yl group which is substituted in the 3 position by anamino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group and mayadditionally be substituted by one or two C₁₋₃-alkyl groups, apiperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the3 position or in the 4 position by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)amino group and may additionally be substituted by one ortwo C₁₋₃-alkyl groups, a 3-amino-piperidin-1-yl group wherein thepiperidin-1-yl-moiety is additionally substituted by an aminocarbonyl,C₁₋₂-alkyl-aminocarbonyl, di-(C₁₋₂-alkyl)-aminocarbonyl,pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl,thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl,piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, a3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety isadditionally substituted in the 4 position or 5 position by a hydroxy ormethoxy group, a 3-amino-piperidin-1-yl group wherein the methylenegroup is replaced in the 2 position or 6 position by a carbonyl group, apiperidin-1-yl or hexahydroazepin-1-yl- group substituted in the 3position by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,wherein two hydrogen atoms on the carbon skeleton of the piperidin-1-ylor hexahydroazepin-1-yl group are each replaced by a straight-chainalkylene bridge, this bridge containing 2 to 5 carbon atoms if the twohydrogen atoms are on the same carbon atom, or 1 to 4 carbon atoms ifthe hydrogen atoms are on adjacent carbon atoms, or 1 to 4 carbon atomsif the hydrogen atoms are on carbon atoms which are separated by oneatom, or 1 to 3 carbon atoms if the hydrogen atoms are on carbon atomswhich are separated by two atoms, an azetidin-1-yl, pyrrolidin-1-yl,piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by anamino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, a piperazin-1-yl or[1,4]diazepan-1-yl group optionally substituted on the carbon skeletonby one or two C₁₋₃-alkyl groups, a 3-imino-piperazin-1-yl,3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl groupoptionally substituted on the carbon skeleton by one or two C₁₋₃-alkylgroups, a [1,4]diazepan-1-yl group optionally substituted by one or twoC₁₋₃-alkyl groups, which is substituted in the 6 position by an aminogroup, a C₃₋₇-cycloalkyl group which is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, a C₃₋₇-cycloalkyl groupwhich is substituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkylor a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, a C₃₋₇-cycloalkyl-C₁₋₂-alkylgroup wherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, aC₃₋₇-cycloalkyl-C₁₋₂-alkyl group wherein the cycloalkyl moiety issubstituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, a C₃₋₇-cycloalkylamino groupwherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, while the two nitrogenatoms on the cycloalkyl moiety are separated from one another by atleast two carbon atoms, an N-(C₃₋₇-cycloalkyl)-N-(C₁₋₃-alkyl)-aminogroup wherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, while the two nitrogenatoms on the cycloalkyl moiety are separated from one another by atleast two carbon atoms, a C₃₋₇-cycloalkylamino group wherein thecycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,an N-(C₃₋₇-cycloalkyl)-N-(C₁ ₃-alkyl)-amino group wherein the cycloalkylmoiety is substituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkylor a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, aC₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino group wherein the cycloalkyl moiety issubstituted by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,an N-(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N-(C₁₋₂-alkyl)-amino group wherein thecycloalkyl moiety is substituted by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)-amino group, a C₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino groupwherein the cycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,an N-(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N-(C₁₋₂-alkyl)-amino group wherein thecycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,an R¹⁹-C₂₋₄-alkylamino group wherein R¹⁹ is separated from the nitrogenatom of the C₂₋₄-alkylamino moiety by at least two carbon atoms and R¹⁹denotes an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, anR¹⁹-C₂₋₄-alkylamino group wherein the nitrogen atom of theC₂₋₄-alkylamino moiety is substituted by a C₁₋₃-alkyl group and R¹⁹ isseparated from the nitrogen atom of the C₂₋₄-alkylamino moiety by atleast two carbon atoms, where R¹⁹ is as hereinbefore defined, an aminogroup substituted by the group R²⁰ wherein R²⁰ denotes an azetidin-3-yl,azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl,pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl,piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl orpiperidin-4-ylmethyl group, while the groups mentioned for R²⁰ may eachbe substituted by one or two C₁₋₃-alkyl groups, an amino groupsubstituted by the group R²⁰ and a C₁₋₃-alkyl group wherein R²⁰ is as Shereinbefore defined, while the groups mentioned for R²⁰ may each besubstituted by one or two C₁₋₃-alkyl groups, an R¹⁹-C₃₋₄-alkyl groupwherein the C₃₋₄-alkyl moiety is straight-chained and may additionallybe substituted by one or two C₁₋₃-alkyl groups, where R¹⁹ is ashereinbefore defined, a 3-amino-2-oxo-piperidin-5-yl or3-amino-2-oxo-1-methyl-piperidin-5-yl group, a pyrrolidin-3-yl,piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl orhexahydroazepin-4-yl group which is substituted in the 1 position by anamino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)amino group, or anazetidin-2-yl-C₁₋₂-alkyl, azetidin-3-yl-C₁₋₂-alkyl,pyrrolidin-2-yl-C₁₋₂-alkyl₃ pyrrolidin-3-yl, pyrrolidin-3-yl-C₁₋₂-alkyl,piperidin-2-yl-C₁₋₂-alkyl, piperidin-3-yl, piperidin-3-yl-C₁₋₂-alkyl,piperidin-4-yl or piperidin-4-yl-C₁₋₂-alkyl group, while theabove-mentioned groups may each be substituted by one or two C₁₋₃-alkylgroups, while by the aryl groups mentioned in the definition of theabove groups are meant phenyl or naphthyl groups, which may be mono- ordisubstituted by R_(h) independently of one another, where thesubstituents are identical or different and R_(h) denotes a fluorine,chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro,amino, aminocarbonyl, aminosulphonyl, methylsulphonyl, acetylamino,methylsulphonylamino, C₁₋₃-alkyl, cyclopropyl, ethenyl, ethynyl,hydroxy, C₁₋₃-alkyloxy, difluoromethoxy or trifluoromethoxy group, bythe heteroaryl groups mentioned in the definitions of theabove-mentioned groups are meant a pyrrolyl, furanyl, thienyl, pyridyl,indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinylgroup, or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one ortwo methyne groups are replaced by nitrogen atoms, or an indolyl,benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group whereinone to three methyne groups are replaced by nitrogen atoms, or a1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl,2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl,1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl,1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl,1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl,2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl,2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl,1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl,1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl,3,4-dihydro-4-oxo-quinazolinyl,1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl,1,2-dihydro-2-oxoquinoxalinyl,1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl,1,2-dihydro-1-oxo-phthalazinyl,1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl,2,3-dihydro-benzo[1,4]dioxinyl or3,4-dihydro-3-oxo-2H-benzo[1,4]oxazinyl group, while the above-mentionedheteroaryl groups may be substituted by R¹⁰ to R¹⁴, where R¹⁰ to R¹⁴ areas hereinbefore defined, and, unless otherwise stated, theabove-mentioned alkyl, alkenyl and alkynyl groups may be straight-chainor branched, as well as the derivatives which are N-oxidised ormethylated or ethylated at the cyclic nitrogen atom in the 3 position or9 position of the hypoxanthine skeleton, as well as the derivativeswherein the 6-oxo group of the hypoxanthine skeleton is replaced by athioxo group, with the proviso that the compounds8-(piperidin-4-ylmethyl)-7-(4-fluorobenzyl)-1,7-dihydro-purin-6-one and8-(1-methyl-piperidin-4-ylmethyl)-7-(4-fluorobenzyl)-1,7-dihydro-purin-6-oneare excluded, the tautomers, enantiomers, diastereomers, the mixturesthereof, the prodrugs thereof and the salts thereof.
 2. The compoundaccording to claim 1, wherein R¹, R² and R³ are defined as in claim 1and R⁴ denotes a pyrrolidin-1-yl group which is substituted in the 3position by an amino group, a piperidin-1-yl group which is substitutedin the 3 position by an amino group, a piperidin-3-yl or piperidin-4-ylgroup, a hexahydroazepin-1-yl group which is substituted in the 3position or 4 position by an amino group, a piperazin-1-yl or[1,4]diazepan-1-yl group, a (2-aminocyclohexyl)amino group, a cyclohexylgroup which is substituted in the 3 position by an amino group, or anN-(2-aminoethyl)-methylamino or an N-(2-aminoethyl)-ethylamino group,the tautomers, enantiomers, diastereomers, the mixtures thereof, theprodrugs and the salts thereof.
 3. The compound according to claim 1,wherein R¹ denotes a hydrogen atom, a C₁₋₆-alkyl group, a C₃₋₆-alkenylgroup, a C₃₋₄-alkynyl group, a C₃₋₆-cycloalkylmethyl group, a phenyl-C1-3-alkyl group wherein the phenyl moiety is substituted by R¹⁰ and R¹¹,where R¹⁰ denotes a hydrogen atom, a fluorine, chlorine or bromine atom,a methyl or trifluoromethyl group, a cyano, aminocarbonyl,dimethylaminocarbonyl or methylsulphonyl group, an amino, acetylamino ormethylsulphonylamino group, a hydroxy, methoxy, difluoromethoxy,trifluoromethoxy, carboxymethoxy, methoxycarbonylmethoxy,ethyloxycarbonylmethoxy, aminocarbonylmethoxy,methylaminocarbonylmethoxy, ethylamino-carbonylmethoxy ordimethylaminocarbonylmethoxy group and R¹¹ denotes a hydrogen atom, afluorine or chlorine atom, or a methyl or methoxy group, anaphthylmethyl group wherein the naphthyl moiety is substituted by R¹⁰and R¹¹, where R¹⁰ and R¹¹ are as hereinbefore defined, aheteroarylmethyl group where the term heteroaryl denotes a furanyl,thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyrimidinyl,pyrazinyl, quinolinyl, isoquinolinyl or quinazolinyl group and theabove-mentioned heteroaryl groups are substituted by R¹⁰ and R¹¹, whereR¹⁰ and R¹¹ are as hereinbefore defined, a phenylcarbonylmethyl groupwherein the phenyl moiety is substituted by R¹⁰ and R¹¹, where R¹⁰ andR¹¹ are as hereinbefore defined, a furanylcarbonylmethyl,thienylcarbonylmethyl or pyridylcarbonylmethyl group, or a 2-oxo-propylor cyclohexylcarbonylmethyl group, R² denotes a hydrogen atom, aC₁₋₆-alkyl group, a C₃₋₆-alkenyl group, a C₃₋₄-alkynyl group, aC₃₋₆-cycloalkyl or C₃₋₆-cycloalkyl-C₁₋₃-alkyl group, a phenyl groupwhich is substituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are ashereinbefore defined, a phenyl-C₁₋₃-alkyl group wherein the phenylmoiety is substituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are ashereinbefore defined, a phenyl-C₂₋₃-alkenyl group wherein the phenylmoiety is substituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are ashereinbefore defined, a phenylcarbonylmethyl group wherein the phenylmoiety is substituted by R¹⁰ and R¹¹, where R¹⁰ and R¹¹ are ashereinbefore defined, a furanyl, thienyl or pyridyl group, afuranyl-C₁₋₃-alkyl, thienyl-C₁₋₃-alkyl or pyridyl-C₁₋₃-alkyl group, acyano group, an amino, C₁₄-alkylamino or di-(C₁₋₄-alkyl)-amino group, anamino group substituted by the groups R¹⁵ and R¹⁶ wherein R¹⁵ denotes ahydrogen atom or a methyl or ethyl group and R¹⁶ denotes a C₁₋₄-alkylgroup which is substituted by a cyano, carboxy, methoxycarbonyl,ethyloxycarbonyl, aminocarbonyl, methylaminocarbonyl,dimethylaminocarbonyl, ethylaminocarbonyl, diethylaminocarbonyl,pyrrolidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group, an amino groupsubstituted by the groups R¹⁵ and R¹⁷ wherein R¹⁵ is as hereinbeforedefined and R¹⁷ denotes a straight-chain C₂₋₄-alkyl group which isterminally substituted in each case by an amino, methylamino,dimethylamino, acetylamino, ethyloxy-carbonylamino, phenylcarbonylamino,methylsulphonylamino, phenylsulphonylamino, hydroxy, methoxy, phenyloxy,methylsulphanyl or phenylsulphanyl group, a pyrrolidin-1-yl,piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or4-methyl-piperazin-1-yl group, a C₃₋₆-cycloalkylamino orC₃₋₆-cycloalkyl-C₁₋₃-alkylamino group, a phenylamino group, aphenyl-C₁₋₃-alkylamino group wherein the phenyl moiety is substituted byR¹⁰ and R¹¹, where R¹⁰ and R¹¹ are as hereinbefore defined, anaphthylmethylamino group, a heteroaryl-C₁₋₂-alkylamino group, where theterm heteroaryl is as hereinbefore defined, or a methylsulphanyl,benzylsulphanyl or (2-phenylethyl)sulphanyl group, R³ denotes aC₄₋₆-alkenyl group, a C₃₋₄-alkenyl group which is substituted by afluorine, chlorine or bromine atom or a trifluoromethyl group, a2-butyl-1-yl group or a methyl group substituted by the group R_(c),where R_(c) denotes a 1-cyclopenten-1-yl-or 1-cyclohexen-1-yl group, aphenyl group optionally substituted by a fluorine, chlorine, bromine oriodine atom, by a methyl, trifluoromethyl, cyano, methoxy,difluoromethoxy or trifluoromethoxy group, a phenyl group which issubstituted by two fluorine atoms, a naphthyl group or a furanyl,thienyl, or pyridyl group, and R⁴ denotes a piperidin-1-yl group whichis substituted in the 3 position by an amino group, ahexahydroazepin-1-yl group which is substituted in the 3 position or 4position by an amino group, a (2-aminocyclohexyl)amino group, acyclohexyl group which is substituted in the 3 position by an aminogroup, or an N-(2-aminoethyl)-methylamino or anN-(2-aminoethyl)-ethylamino group, while unless otherwise stated, theabove-mentioned alkyl, alkenyl and alkynyl groups may be straight-chainor branched.
 4. The compound according to claim 3, wherein R¹ denotes ahydrogen atom, a methyl, benzyl or 2-phenylethyl group, a naphthylmethylor methoxynaphthylmethyl group or a phenylcarbonylmethyl group, R²denotes a hydrogen atom, a methyl or 2-phenylethyl group, aphenylcarbonylmethyl group, a cyano group, an amino, methylamino,dimethylamino, isopropylamino, cyclohexylamino- or(cyclohexylmethyl)amino group, a benzylamino, fluorob enzyl amino or(2-phenylethyl) amino group or a piperidin-1-yl group, R³ denotes abenzyl or 3-methyl-but-2-en-1-yl group and R⁴ denotes a(3-amino-piperidin-1-yl) group.
 5. A compound chosen from: (1)8-(3-amino-piperidin-1-yl)-7-benzyl-2-benzylamino-1-methyl-1,7-dihydro-purin-6-one,(2)8-(3-amino-piperidin-1-yl)-7-benzyl-2-(4-fluoro-benzylamino)-1-methyl-1,7-dihydro-purin-6-one,(3)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-[(2-phenylethyl)amino]-1,7-dihydro-purin-6-one,(4)8-(3-amino-piperidin-1-yl)-7-benzyl-2-isopropylamino-1-methyl-1,7-dihydro-purin-6-one,(5)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methylamino-1,7-dihydro-purin-6-one,(6)8-(3-amino-piperidin-1-yl)-7-benzyl-2-cyclohexylamino-1-methyl-1,7-dihydro-purin-6-one,(7) 8-(3-amino-piperidin-1-yl)-7-benzyl-2-[(cyclohexylmethyl)amino]-1-methyl-1,7-dihydro-purin-6-one, (8)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-(piperidin-1-yl)-1,7-dihydro-purin-6-one,(9)8-(3-amino-piperidin-1-yl)-7-benzyl-2-dimethylamino-1-methyl-1,7-dihydro-purin-6-one,(10)2-amino-8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-1,7-dihydro-purin-6-one,(11)8-(3-amino-piperidin-1-yl)-2-benzylamino-1-methyl-7-(3-methyl-but-2-en-1-yl)-1,7-dihydro-purin-6-one,(12) 8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-2-methyl- l,7-dihydro-purin-6-one, (13)8-(3-amino-piperidin-1-yl)-1-methyl-7-(3-methyl-but-2-en-1-yl)-2-(2-phenyl-ethyl)-1,7-dihydro-purin-6-one,(14)8-(3-amino-piperidin-1-yl)-7-benzyl-1-methyl-1,7-dihydro-purin-6-one,(15)8-(3-amino-piperidin-1-yl)-7-benzyl-1-(2-oxo-2-phenyl-ethyl)-1,7-dihydro-purin-6-one,(16)8-(3-amino-piperidin-1-yl)-2-methyl-7-(3-methyl-but-2-en-1-yl)-1-[(naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-one,(17)8-(3-amino-piperidin-1-yl)-7-(3-methyl-but-2-en-1-yl)-1-[(naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-oneand (18)8-(3-amino-piperidin-1-yl)-7-(3-methyl-but-2-en-1-yl)-1-[(4-methoxy-naphthalen-1-yl)methyl]-1,7-dihydro-purin-6-oneas well as the tautomers, enantiomers, diastereomers, the mixturesthereof and the salts thereof.
 6. A physiologically acceptable salt of acompound according to claim 1 with inorganic or organic acids or bases.7. A pharmaceutical composition comprising a pharmaceutically effectiveamount of a compound according to claim 1 optionally together with oneor more pharmaceutically acceptable inert carriers and/or diluents.
 8. Amethod of treating type I and type II diabetes mellitus, arthritis,obesity, allograft transplantation or calcitonin-induced osteoporosis,said method comprising administering to a patient in need thereof apharmaceutically effective amount of a compound according to claim 1.